Rigmor Solberg

• Forbord, Karl Martin; Okla, Meshail; Lunde, Ngoc Nguyen; Bosnjak, Tatjana; Arnekleiv, Guro Lorvik & Hesselson, Daniel [Vis alle 11 forfattere av denne artikkelen] (2023). The Cysteine Protease Legumain Is Upregulated by Vitamin D and Is a Regulator of Vitamin D Metabolism in Mice. Cells. ISSN 2073-4409. 13(1). doi: 10.3390/cells13010036. Fulltekst i vitenarkiv Vis sammendrag

  Legumain is a lysosomal cysteine protease that has been implicated in an increasing amount of physiological and pathophysiological processes. However, the upstream mechanisms regulating the expression and function of legumain are not well understood. Here, we provide in vitro and in vivo data showing that vitamin D3 (VD3) enhances legumain expression and function. In turn, legumain alters VD3 bioavailability, possibly through proteolytic cleavage of vitamin D binding protein (VDBP). Active VD3 (1,25(OH)2D3) increased legumain expression, activity, and secretion in osteogenic cultures of human bone marrow stromal cells. Upregulation of legumain was also observed in vivo, evidenced by increased legumain mRNA in the liver and spleen, as well as increased legumain activity in kidneys from wild-type mice treated with 25(OH)D3 (50 µg/kg, subcutaneously) for 8 days compared to a control. In addition, the serum level of legumain was also increased. We further showed that active legumain cleaved purified VDBP (55 kDa) in vitro, forming a 45 kDa fragment. In vivo, no VDBP cleavage was found in kidneys or liver from legumain-deficient mice (Lgmn−/−), whereas VDBP was cleaved in wild-type control mice (Lgmn+/+). Finally, legumain deficiency resulted in increased plasma levels of 25(OH)D3 and total VD3 and altered expression of key renal enzymes involved in VD3 metabolism (CYP24A1 and CYP27B1). In conclusion, a regulatory interplay between VD3 and legumain is suggested.

• Lunde, Ngoc Nguyen; Osoble, Nimo Mukhtar Mohamud; Dalmao-Fernandez, Andrea; Lukacs, Alfreda Serwah; Jafari, Abbas & Singh, Sachin [Vis alle 10 forfattere av denne artikkelen] (2023). Interplay between Cultured Human Osteoblastic and Skeletal Muscle Cells: Effects of Conditioned Media on Glucose and Fatty Acid Metabolism. Biomedicines. 11:2908(11), s. 1–20. doi: 10.3390/biomedicines11112908. Fulltekst i vitenarkiv
• Solberg, Rigmor; Lunde, Ngoc Nguyen; Forbord, Karl Martin Frøseth; Okla, Meshail; Kassem, Moustapha & Jafari, Abbas (2022). The Mammalian Cysteine Protease Legumain in Health and Disease. International Journal of Medical Sciences. ISSN 1449-1907. 23(24). doi: 10.3390/ijms232415983. Fulltekst i vitenarkiv Vis sammendrag

  The cysteine protease legumain (also known as asparaginyl endopeptidase or δ-secretase) is the only known mammalian asparaginyl endopeptidase and is primarily localized to the endolysosomal system, although it is also found extracellularly as a secreted protein. Legumain is involved in the regulation of diverse biological processes and tissue homeostasis, and in the pathogenesis of various malignant and nonmalignant diseases. In addition to its proteolytic activity that leads to the degradation or activation of different substrates, legumain has also been shown to have a nonproteolytic ligase function. This review summarizes the current knowledge about legumain functions in health and disease, including kidney homeostasis, hematopoietic homeostasis, bone remodeling, cardiovascular and cerebrovascular diseases, fibrosis, aging and senescence, neurodegenerative diseases and cancer. In addition, this review addresses the effects of some marketed drugs on legumain. Expanding our knowledge on legumain will delineate the importance of this enzyme in regulating physiological processes and disease conditions.

• Nielsen, Erik Waage; Miller, Yoav; Brekke, Ole Lars; Grond, Joost; Duong, Anh Hoang & Fure, Hilde [Vis alle 12 forfattere av denne artikkelen] (2022). A Novel Porcine Model of Ischemia-Reperfusion Injury After Cross-Clamping the Thoracic Aorta Revealed Substantial Cardiopulmonary, Thromboinflammatory and Biochemical Changes Without Effect of C1-Inhibitor Treatment. Frontiers in Immunology. ISSN 1664-3224. 13:852119, s. 1–12. doi: 10.3389/fimmu.2022.852119. Fulltekst i vitenarkiv
• Gregersen, Ida; Michelsen, Annika; Lunde, Ngoc Nguyen; Åkerblom, Axel; Lakic, Tatevik G. & Skjelland, Mona [Vis alle 20 forfattere av denne artikkelen] (2020). Legumain in Acute Coronary Syndromes: A Substudy of the PLATO (Platelet Inhibition and Patient Outcomes) Trial. Journal of the American Heart Association (JAHA). ISSN 2047-9980. e016360. doi: 10.1161/JAHA.120.016360. Fulltekst i vitenarkiv
• Lunde, Ngoc Dieu Nguyen; Gregersen, Ida; Ueland, Thor; Shetelig, Christian; Holm, Sverre & Kong, Xiang Yi [Vis alle 31 forfattere av denne artikkelen] (2019). Legumain is upregulated in acute cardiovascular events and associated with improved outcome – potentially related to anti-inflammatory effects on macrophages. Atherosclerosis. ISSN 0021-9150. s. 1–9. doi: 10.1016/j.atherosclerosis.2019.12.008. Fulltekst i vitenarkiv
• Lunde, Ngoc Dieu Nguyen; Bosnjak, Tatjana; Solberg, Rigmor & Johansen, Harald Thidemann (2019). Mammalian legumain - A lysosomal cysteine protease with extracellular functions? Biochimie. ISSN 0300-9084. 166, s. 77–83. doi: 10.1016/j.biochi.2019.06.002. Vis sammendrag

  The cysteine protease legumain (asparaginyl endopeptidase, AEP) plays important roles in normal physiology but is also associated with several disorders, such as atherosclerosis, osteoporosis, cancer and neurodegenerative diseases. The functional roles of legumain have mainly been associated with the presence in lysosomes where legumain is active and mediates processing of multiple proteins, such as the conversion of single to double chain forms of cysteine cathepsins. However, in recent years, a number of studies point to extracellular roles of legumain in addition to the pivotal roles in the lysosomes. In this review, recent knowledge on novel extracellular functions of this protease will be addressed and new discoveries in relation to the diseases mentioned above will be presented.

• Bosnjak, Tatjana; Solberg, Rigmor; Hemati, Paya Diana; Jafari, Abbas; Kassem, Moustapha & Johansen, Harald Thidemann (2019). Lansoprazole inhibits the cysteine protease legumain by binding to the active site. Basic & Clinical Pharmacology & Toxicology. ISSN 1742-7835. 125(2), s. 89–99. doi: 10.1111/bcpt.13230.
• Lunde, Ngoc Nguyen Dieu; Haugen, Mads Haugland; Larsen, Kristina Broe Bodin; Damgaard, Ingrid; Pettersen, Solveig & Kasem, Roya [Vis alle 11 forfattere av denne artikkelen] (2017). Glycosylation is important for legumain localization and processing to active forms but not for cystatin E/M inhibitory functions. Biochimie. ISSN 0300-9084. 139, s. 27–37. doi: 10.1016/j.biochi.2017.05.009.
• Jafari, Abbas; Qanie, Diyako; Andersen, Thomas L.; Zhang, Yuxi; Chen, Li & Postert, Benno [Vis alle 16 forfattere av denne artikkelen] (2017). Legumain regulates differentiation fate of human bone marrow stromal cells and is altered in postmenopausal osteoporosis. Stem Cell Reports. ISSN 2213-6711. 8(2), s. 373–386. doi: 10.1016/j.stemcr.2017.01.003. Fulltekst i vitenarkiv
• Lunde, Ngoc Nguyen Dieu; Holm, Sverre; Dahl, Tuva Børresdatter; Inass, Elyouncha; Sporsheim, Bjørnar & Gregersen, Ida [Vis alle 12 forfattere av denne artikkelen] (2017). Increased levels of legumain in plasma and plaques from patients with carotid atherosclerosis. Atherosclerosis. ISSN 0021-9150. 257, s. 216–223. doi: 10.1016/j.atherosclerosis.2016.11.026. Fulltekst i vitenarkiv Vis sammendrag

  Background and aims The cysteine protease legumain has been shown to be up-regulated in unstable atherosclerotic plaques. This study aims to further elucidate legumain in atherosclerosis, by examining legumain in plasma and carotid plaques from patients with carotid stenosis. Furthermore, legumain secretion from monocyte-derived macrophages treated with atherogenic lipids during macrophage polarization was studied. Methods Plasma levels of legumain from patients with carotid stenosis (n = 254), healthy controls (n = 91), and secreted from monocyte-derived macrophages were assessed by enzyme-linked-immunosorbent assay. Quantitative PCR and immunoblotting of legumain were performed on isolated plaques and legumain localization was visualized by immunohistochemistry and fluorescence microscopy. Monocyte-derived macrophages polarized to M1 or M2 macrophages were treated with VLDL, oxLDL or cholesterol crystals (CC) and the level of legumain analysed. Results Patients with carotid stenosis had significantly higher levels of plasma legumain compared with healthy controls (median 2.0 versus 1.5 ng/ml, respectively; p = 0.003), although there was no correlation between the level of legumain and the degree of stenosis, and legumain was not an independent factor to identify patients with carotid plaques. Moreover, patients with symptoms the last 2 months had higher expressions of mature legumain, cystatin C and E/M, and the macrophage markers CD80 (M1) and CD163 (M2). Legumain co-localized with both M1 and M2 macrophages within plaques, whereas legumain mRNA expression was significantly higher (p < 0.0001) in plaques compared to non-atherosclerotic arteries (controls). Furthermore, in vitro studies showed significantly increased secretion of legumain from pro-inflammatory M1 compared to pro-resolving M2 macrophages (p = 0.014), and particularly in M1 treated with CC. In plaques, legumain was localized to structures resembling foam cells. Conclusions Legumain is increased in both plasma and plaques of patients with carotid stenosis and might be a new and early biomarker of atherosclerosis.

• Poreba, Marcin; Solberg, Rigmor; Rut, Wioletta; Lunde, Ngoc Nguyen Dieu; Kasperkiewicz, Paulina & Snipas, Scott J. [Vis alle 11 forfattere av denne artikkelen] (2016). Counter selection substrate library strategy for developing specific protease substrates and probes. Cell Chemical Biology. ISSN 2451-9456. 23(8), s. 1023–1034. doi: 10.1016/j.chembiol.2016.05.020.
• Solberg, Rigmor; Smith, Robert; Almlöf, Maria; Tewolde, Eyassu Araia; Nilsen, Hilde & Johansen, Harald Thidemann (2014). Legumain expression, activity and secretion are increased during monocyte-to-macrophage differentiation and inhibited by atorvastatin. Biological chemistry. ISSN 1431-6730. 396(1), s. 71–80. doi: 10.1515/hsz-2014-0172.
• Solberg, Rigmor; Smith, Robert; Almlöf, Maria; Tewolde, Eyassu Araia; Nilsen, Hilde & Johansen, Harald Thidemann (2014). Atorvastatin inhibits processing, activity and secretion of legumain in macrophages. Biological chemistry. ISSN 1431-6730. 396(1), s. 71–80. doi: 10.1515/hsz-2014-0172.
• Smith, Robert; Åstrand, Ove Alexander Høgmoen; Nguyen, Luan Minh; Elvestrand, Tina; Hagelin, Gunnar & Solberg, Rigmor [Vis alle 8 forfattere av denne artikkelen] (2014). Synthesis of a novel legumain-cleavable colchicine prodrug with cell-specific toxicity. Bioorganic & Medicinal Chemistry. ISSN 0968-0896. 22(13), s. 3309–3315. doi: 10.1016/j.bmc.2014.04.056.
• Smith, Robert; Solberg, Rigmor; Jacobsen, Linn Løkken; Voreland, Anette Larsen; Rustan, Arild & Thoresen, G. Hege [Vis alle 7 forfattere av denne artikkelen] (2014). Simvastatin inhibits glucose metabolism and legumain activity in human myotubes. PLOS ONE. ISSN 1932-6203. 9(1:85721). doi: 10.1371/journal.pone.0085721.
• Berven, Lise; Johansen, Harald Thidemann; Solberg, Rigmor; Kolset, Svein Olav & Samuelsen, Anne Berit C. (2013). Autoactivation of prolegumain is accelerated by glycosaminoglycans. Biochimie. ISSN 0300-9084. 95(4), s. 772–781. doi: 10.1016/j.biochi.2012.11.002. Vis sammendrag

  The cysteine protease legumain participates in several biological and pathological processes including tumour invasion and metastasis. Legumain is synthesized as a zymogen and undergoes pH-dependent autoactivation of the proform in order to reach an enzymatically active form. Here we demonstrate that the naturally occurring polyanionic glycosaminoglycans (GAGs) chondroitin 4-sulphate (C4S), chondroitin 6-sulphate (C6S), chondroitin 4,6-sulphate (C4,6S), heparin, heparan sulphate (HS) as well as chondroitin sulphate (CS)-derived decasaccharides accelerated the autocatalytic activation of prolegumain through ionic interactions in a concentration-, size- and time-dependent manner at pH 4.0. In contrast, at pH 5.0 only C4S and C4,6S were able to promote prolegumain activation, while CS-derived decasaccharides, C6S, heparin and HS lost their effect at this pH.

• Berven, Lise; Solberg, Rigmor; Truong, Hoa Hong Thi; Arlov, Øystein; Aachmann, Finn Lillelund & Skjåk-Bræk, Gudmund [Vis alle 9 forfattere av denne artikkelen] (2013). Alginates induce legumain activity in RAW 264.7 cells and accelerate autoactivation of prolegumain. Bioactive Carbohydrates and Dietary Fibre. ISSN 2212-6198. 2, s. 30–44. doi: 10.1016/j.bcdf.2013.08.003.
• Haugen, Mads Haugland; Johansen, Harald Thidemann; Pettersen, Solveig; Solberg, Rigmor; Brix, Klaudia & Flatmark, Kjersti [Vis alle 7 forfattere av denne artikkelen] (2013). Nuclear Legumain Activity in Colorectal Cancer. PLOS ONE. ISSN 1932-6203. 8(1). doi: 10.1371/journal.pone.0052980. Fulltekst i vitenarkiv
• Smith, Robert; Johansen, Harald Thidemann; Nilsen, Hilde; Haugen, Mads Haugland; Pettersen, Solveig & Mælandsmo, Gunhild [Vis alle 8 forfattere av denne artikkelen] (2012). Intra- and extracellular regulation of activity and processing of legumain by cystatin E/M. Biochimie. ISSN 0300-9084. 94(12), s. 2590–2599. doi: 10.1016/j.biochi.2012.07.026.
• Johansen, Harald Thidemann & Solberg, Rigmor (2012). Extracellular functions of cystein proteases. I Karamanos, Nikos K (Red.), Extracellular matrix: Pathobiology and signaling. Walter de Gruyter (De Gruyter). ISSN 978-3-11-025876-9. s. 239–260. doi: 10.1515/9783110258776.239.
• Briggs, Jon; Haugen, Mads Haugland; Johansen, Harald Thidemann; Riker, Adam I; Abrahamson, Magnus & Fodstad, Øystein [Vis alle 8 forfattere av denne artikkelen] (2010). Cystatin E/M suppresses legumain activity and invasion of human melanoma. BMC Cancer. ISSN 1471-2407. 10(1). doi: 10.1186/1471-2407-10-17.
• Solberg, Rigmor; Aas, Vigdis; Thoresen, G. Hege; Kase, Eili Tranheim; Drevon, Christian A & Rustan, Arild [Vis alle 7 forfattere av denne artikkelen] (2005). Leptin expression in human primary skeletal muscle cells is reduced during differentiation. Journal of Cellular Biochemistry. ISSN 0730-2312. 96(1), s. 89–96.
• Aas, Vigdis; Kase, Eili Tranheim; Solberg, Rigmor; Jensen, Jørgen & Rustan, Arild (2004). Chronic hyperglycaemia promotes lipogenesis and triacylglycerol accumulation in human skeletal muscle cells. Diabetologia. ISSN 0012-186X. 47, s. 1452–1461.
• Yaqub, Sheraz; Solhaug, Vigdis; Vang, Torkel; Solberg, Rigmor; Aasen, Ansgar Oddne & Tasken, Kjetil [Vis alle 7 forfattere av denne artikkelen] (2003). A human whole blood model of LPS-mediated suppression of T-cell activation. Medical Science Monitor. ISSN 1234-1010. 9(BR), s. 120–126.
• Yaqub, Sheraz; Solhaug, Vigdis; Vang, Torkel; Solberg, Rigmor; Aasen, Ansgar Oddne & Tasken, Kjetil [Vis alle 7 forfattere av denne artikkelen] (2003). A human whole blood model of LPS mediated suppression on T cell activation. Medical Science Monitor. ISSN 1234-1010. s. 120–126.
• Saugstad, Ola Didrik; Ramji, S; Irani, S. F.; El-Meneza, S; Hernandez, E. A. & Vento, M [Vis alle 10 forfattere av denne artikkelen] (2003). Resuscitation of newborn infants with 21% or 100% oxygen: follow-up at 18 to 24 months. Pediatrics. ISSN 0031-4005. 11(2), s. 296–300. Vis sammendrag

  esuscitation of newborn infants with 21% or 100% oxygen: follow-up at 18 to 24 months. Saugstad OD, Ramji S, Irani SF, El-Meneza S, Hernandez EA, Vento M, Talvik T, Solberg R, Rootwelt T, Aalen OO. Department of Pediatric Research, Rikshospitalet, University of Oslo, Oslo, Norway. o.d.saugstad@klinmed.uio.no OBJECTIVE: To follow-up children who had been resuscitated at birth with either 21% or 100% oxygen (O2). METHODS: A multicenter study with 10 participating centers recruited 609 infants to the Resair 2 study where resuscitation was performed with either 21% or 100% O2. A follow-up between ages 18 and 24 months was performed. However, during follow-up registration, it was found that 18 infants had been enrolled twice in the original Resair 2 study with different registration numbers, leaving 591 enrolled in the Resair 2 study and 410 enrolled in the 7 centers participating in the follow-up. Of these 410 infants, 79 died (76 in the neonatal and 3 in the postneonatal period). Furthermore, for 8 infants informed consent was not obtained, leaving 323 eligible for follow-up. Of these, 213 infants (66%) were followed-up: 91 (62%) had been resuscitated with 21% O2, and 122 (69%) with 100% O2. At a median age of 22 and 20 months (not significant) in the 21% and 100% groups, respectively, a simple questionnaire was filled out and neurologic assessment was performed in addition to measuring anthropometric data. RESULTS: There were no significant differences in weight, height, or head circumference between the 2 groups. Cerebral palsy developed in 10% and 7%, respectively, in the 2 groups (not significant). In total, 11 cases (12%) in the 21% versus 11 cases (9%) in the 100% O(2) group (odds ratio: 1.39, 95% confidence interval: 0.57-3.36) developed cerebral palsy and/or mental or other delay. Furthermore, it was concluded that 14 (15%) in the 21% group and 12 (10%) in the 100% group were not normal (odds ratio: 1.67, 95% confidence interval: 0.73-3.80). CONCLUSIONS: There were no significant differences in somatic growth or neurologic handicap at an age of 18 to 24 months in infants resuscitated with either 21% or 100% O2 at birth. Based on these data, resuscitation with ambient air seems to be safe, at least in most cases. More studies are needed to settle this issue.

• Scholz, Tim; Solberg, Rigmor; Okkenhaug, Cecilie; Videm, Vibeke; Gallimore, Michael J. & Mathisen, Øystein [Vis alle 11 forfattere av denne artikkelen] (2002). The significance of heparin-coated veno-venous bypass circuits in liver transplantation. Perfusion. ISSN 0267-6591. 17, s. 45–50.
• Scholz, Tim; Solberg, Rigmor; Okkenhaug, Cecilie; Videm, Vibeke; Gallimore, Michael J. & Mathisen, Øystein [Vis alle 12 forfattere av denne artikkelen] (2001). Veno-venous bypass in liver transplantation: heparin-coated perfusion circuits reduce the activation of humoral defense systems in an in vitro model. Perfusion. ISSN 0267-6591. 16(4), s. 285–292. Vis sammendrag

  We studied the effects of bypass circuit surface heparinization on kallikrein-kinin, coagulation, fibrinolytic and complement activation in a closed model system for simulating veno-venous bypass (VVBP) in liver transplantation (OLT). The circuits were identical to those in routine use during clinical OLT in our institution. Fresh whole human blood diluted 1:2 with Ringer's acetate was circulated at non-pulsatile flow (2 L/min) and at a constant temperature (37.5°C) for 12 hours. In 10 experiments, the entire inner surface of the circuits was coated with end-point attached heparin (HC). In the remaining 10, non-treated PVC tubings were used (NC). Components of the plasma kallikrein-kinin, coagulation, fibrinolytic and complement systems were analyzed using functional techniques (chromogenic peptide substrate assays) and enzyme immunoassays at baseline, 3 and 12 h. Significant activation of the initial (C3bc) and terminal (TCC) components of the complement system was found in both the NC and HC groups after 3 and 12 h: C3bc: NC: baseline = 4 (3.5-7.7), 3 h = 17.3* (12.5-27), 12 h = 31* (17.7-63.6), HC: baseline = 4.9 (3.2-6.8), 3 h = 9* (6-14.4), 12 h = 13.7* (7.4-18.1). TCC: NC: baseline = 0.4 (0.2-0.6), 3 h = 5* (0.8-11.9), 12 h: 13.1* (4.2-25.7). HC: baseline = 0.5 (0.1-0.6), 3 h = 0.6* (0.1-0.8), 12 h = 1.2* (0.3-2) AU/ml; median and range, (*: p<0.05). The C3bc and TCC concentrations were significantly higher in the NC group at 3 and 12 h, compared to the HC group: C3bc (NC vs. HC group): 3 h, p<0.001; 12 h, p<0.001. TCC (NC vs. HC group): 3 h, p<0.001; 12 h, p<0.001. Significant increases in values of thrombin-antithrombin complexes (p=0.003), prothrombin fragment 1+2 (p=0.006) and plasmin-a2-antiplasmin complexes (p=0.016) were found in the non-coated group, but not in the heparin-coated group during the observation period, showing that also the coagulation and fibrinolytic systems were activated in the non-coated circuits. We conclude that heparin-coating of the internal surface of the extracorporeal perfusion circuit used for VVBP reduces activation of the plasma cascade systems in a closed venous system in vitro.

• Wang, Jacob Edward; Jørgensen, Pål Foyn; Almlöf, Maria; Thiemmermann, Christoph; Foster, Simon J & Aasen, Ansgar Oddne [Vis alle 7 forfattere av denne artikkelen] (2001). Peptidoglycan primes for the LPS-induced release of proinflammatory cytokines in whole human blood. Shock. ISSN 1073-2322. 16(3), s. 178–182.
• Jørgensen, Pål Foyn; Wang, Jacob Edward; Almlöf, Mia; Solberg, Rigmor; Okkenhaug, Cecilie & Scholz, Tim [Vis alle 9 forfattere av denne artikkelen] (2001). Sirolimus interferes with innate response to bacterial products in human whole blood by attenuation of IL-10 production. Scandinavian Journal of Immunology. ISSN 0300-9475. 53, s. 184–191. Vis sammendrag

  Current immunosuppressive strategies are aimed at abrogating the allospecific T-cell response against donor tissue or organs. However, little information is yet available on the potential influence of these drugs on innate immune responses. In order to address this, we have employed a whole blood model. Human whole blood was pretreated with sirolimus, cyclosporine A or tacrolimus in therapeutic as well as supra therapeutic doses, and subsequently stimulated with lipopolysaccharide (LPS), peptidoglycan (PepG), or lipoteichoic acid (LTA). Plasma cytokine analyses revealed a potent inhibitory effect of sirolimus on interleukin (IL)-10 production induced by all bacterial products. In contrast, cyclosporine A and tacrolimus inhibited the tumor necrosis factor (TNF)-a production in response to LPS, but not to PepG and LTA. Using a quantitative mRNA analyses, we also observed that sirolimus significantly decreased the IL-10 mRNA accumulation to sub-basal levels in the peripheral blood mononuclear cells (PBMC). This suggests that sirolimus inhibits IL-10 production by interfering with the IL-10 gene transcription. However, the molecular mechanism of this inhibition remains unclear. Based on the present study and observations by others, we postulate that thye clinical use of sirolimus may be associated with a dysregulated innate immune response to bacterial infection and thus an increased risk of hyperinflammation and sepsis.

• Jørgensen, Pål Foyn; Wang, Jacob Edward; Almlöf, Mia; Thiemmermann, Christoph; Foster, Simon J & Solberg, Rigmor [Vis alle 7 forfattere av denne artikkelen] (2001). Peptidoglycan and lipoteichoic acid modify monocyte phenotype in human whole blood. Clinical and Laboratory Immunology. ISSN 1071-412X. 8(3), s. 515–521. Vis sammendrag

  We examined the influence of the gram-positive cell wall products peptidoglycan (PepG) and lipoteichoic acid (LTA), compared to lipopolysaccharide (LPS), on the monocyte expression of receptors involved in antigen presentation (HLA-DR, B7.1, and B7.2), cell adhesion (ICAM-1 and LFA-3),phagocytosis (FcgRI), and cell activation (CD14). We also evaluated possible influences of the immunosuppressive drugs cyclosporine A, tacrolimus and sirolimus on the expression of these receptors. Pretreatment of whole blood for 4h with the immunosuppressive drugs did not influence the expression of the surface receptors in normal or stimulated blood. Stimulation with both PepG and LTA caused significant up-regulation of the surface expression of ICAM-1 and HLA-DR on whole blood monocytes, similar to that obtained with LPS, whereas B7.1, B7.2, LFA-3 and FcgRI were not modulated. PepG and LTA also caused increased expression of CD14, whereas LPS down-regulated this molecule. In contrast, we did not detect any significant influence of any of the bacterial products on the plasma concentration of soluble CD14. We hypothesized that the increased expression of surface CD14 in blood stimulated with PepG would prime for cellular activation by LPS. Indeed, we show that PepG and the partial PepG structure muramyl dipeptide acted in synergy with LPS to cause the release of TNF-a. The results suggest that PepG and LPS provoke partly different responses on monocyte phenotype and that CD14 may play different roles in the innate response to gram-positive and gram-negative bacteria.

• Jørgensen, Pål Foyn; Wang, Jacob Edward; Solberg, Rigmor; Thiemmermann, Christoph; Foster, Simon J & Aasen, Ansgar Oddne (2001). Procalcitonin does not influence the surface expression of inflammatory receptors on whole blood leukocytes. Intensive Care Medicine. ISSN 0342-4642. 27(2), s. 430–433. Vis sammendrag

  The plasma levels of procalcitonin (PCT) are increased in patients with severe bacterial infections. Its cellular origin and potential pathophysiological function in sepsis is, however, unclear. White blood cells have recently been described to express both PCT mRNA and protein. The aim of this study was to determine whether PCT has any influence on the surface expression of receptors, relevant in inflammation, on human whole blood leukocytes under normal and septic conditions. Venous blood from healthy donors was incubated with PCT (40 ng/ml or 1200 ng/ml) alone or in combination with lipopolysaccharide (LPS, 10 ng/ml) or peptidoglycan (PepG, 10 mg/ml) for 6 hours. The surface expression of CD14, CD54, CD64, CD80, CD86 and HLA-DR was determined by flow cytometry. We could not detect any influence of PCT on the expression of these receptors. Further studies on potential effects on other cell types during infection seem warranted.

• Scholz, Tim; Solberg, Rigmor; Okkenhaug, Cecilie; Videm, Vibeke; Gallimore, J Michael & Mathisen, Øystein [Vis alle 12 forfattere av denne artikkelen] (2001). Veno-venous bypass in liver transplantation: heparin coated perfusion circuits reduce the activation of humoral defence systems in an in vitro model. Perfusion. ISSN 0267-6591. s. 285–292.

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• Thoresen, G. Hege; Simonsen, terje; Christensen, Hege; Johansen, Harald Thidemann; Kase, Eili Tranheim & Robertsen, Ida [Vis alle 9 forfattere av denne artikkelen] (2021). Basal farmakologi. Fagbokforlaget. ISBN 9788245033557. 405 s.
• Thoresen, G. Hege; Solberg, Rigmor; Johansen, Harald Thidemann; Kase, Eili Tranheim; Rustan, Arild Christian & Christensen, Hege [Vis alle 7 forfattere av denne artikkelen] (2020). Illustrert farmakologi. Fagbokforlaget. ISBN 9788245033564. 392 s.

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• Solberg, Rigmor (2023). Drugs and new pharmacological targets in the treatment of osteoporosis .
• Alrawaf, Firas; Nilsen, Hilde; Lunde, Ngoc Nguyen; Morland, Cecilie & Solberg, Rigmor (2022). The cysteine protease legumain in Parkinson’s disease.
• Antobreh, Alfreda Serwah; Lunde, Ngoc Nguyen; Nilsen, Hilde & Solberg, Rigmor (2022). Effects of conditioned media from skeletal muscle cells on metabolism and regulation of the cysteine protease legumain in differentiating osteoblasts.
• Ciyow, Nasra; Bosnjak, Tatjana; Nilsen, Hilde; Lunde, Ngoc Nguyen; Johansen, Harald Thidemann & Solberg, Rigmor (2020). Effekt av teriparatid på differensiering og regulering av cysteinproteaser i osteoblaster.
• Olsen, Kristine Løkke; Johansen, Harald Thidemann; Nilsen, Hilde; Solberg, Rigmor & Berg, Kristian (2020). Effekt av cysteinproteasen legumain på celleviabilitet etter fotodynamisk terapi.
• Mohanachandran, Arthii; Bosnjak, Tatjana; Nilsen, Hilde; Lunde, Ngoc Nguyen; Solberg, Rigmor & Johansen, Harald Thidemann (2020). Differensiering av RAW264.7 til osteoklaster og karakterisering av cysteinproteaser i osteoklaster.
• Solberg, Rigmor (2019). The proteolytic enzyme legumain: Structure and functions.
• Bosnjak, Tatjana; Solberg, Rigmor; Arnekleiv, Guro L.; Nilsen, Hilde; Jafari, Abbas & Bassatne, A. [Vis alle 9 forfattere av denne artikkelen] (2019). Vitamin D3 upregulates legumain in the early phase of osteoblast differentiation .
• Awale, Mustafa; Bosnjak, Tatjana; Nilsen, Hilde; Solberg, Rigmor & Johansen, Harald Thidemann (2019). Effekten av kjønnshormoner på differensiering av stamceller til osteoblaster og regulering av cysteinproteasene legumain og cathepsin B.
• Lunde, Ngoc Nguyen Dieu; Holm, Sverre; Dahl, Tuva Børresdatter; Elyouncha, Inass; Sporsheim, Bjørnar & Gregersen, Ida [Vis alle 12 forfattere av denne artikkelen] (2018). Plasma and plaques from patients with carotid atherosclerosis have increased levels of legumain .
• Solberg, Rigmor (2018). Hvordan settes positive dopinganalyser i medisinsk/farmakologisk sammenheng, og hvordan omsettes dette til dom?
• Bosnjak, Tatjana; Hemati, Paya Diana; Solberg, Rigmor & Johansen, Harald Thidemann (2018). Cysteine proteases as Targets for Proton Pump Inhibitors (PPIs).
• Lunde, Ngoc Nguyen Dieu; Gregersen, Ida; Holm, Sverre; Michelsen, Annika; Sporsheim, Bjørnar & Espevik, Terje [Vis alle 9 forfattere av denne artikkelen] (2018). Platelet-derived legumain, a cysteine protease involved in atherosclerosis .
• Abbas, Iram; Nilsen, Hilde; Johansen, Harald Thidemann & Solberg, Rigmor (2018). Deksametason hemmer differensiering av humane mesenkymale stamceller til osteoblaster og regulerer cysteinproteasene legumain og cathepsin B.
• Gjonbalaj, Nora; Nilsen, Hilde; Solberg, Rigmor & Johansen, Harald Thidemann (2018). Effekt av inflammasjon på regulering av cysteinproteasene legumain og cathepsin B under differensiering av humane mesenkymale stamceller til osteoblaster.
• Solberg, Rigmor; Bosnjak, Tatjana; Nilsen, Hilde; Jafari, Abbas; Kassem, Moustapha & Johansen, Harald Thidemann (2017). Regulation of legumain and cysteine cathepsins during differentiation of human bone marrow stromal cells towards osteoblasts.
• Bosnjak, Tatjana; Hemati, Paya Diana; Nilsen, Hilde; Solberg, Rigmor & Johansen, Harald Thidemann (2017). Legumain as a target for proton pump inhibitors (PPIs): Importance for off-target effects of PPIs?
• Lunde, Ngoc Nguyen Dieu; Holm, Sverre; Dahl, Tuva B.; Elyoncha, Inass; Sporsheim, Bjørnar & Gregersen, Ida [Vis alle 12 forfattere av denne artikkelen] (2017). Plasma and plaques from patients with carotid atherosclerosis have increased levels of legumain.
• Arnekleiv, Guro L.; Nilsen, Hilde; Lunde, Ngoc Nguyen Dieu; Solberg, Rigmor & Johansen, Harald Thidemann (2017). Effekt av vitamin D3 på uttrykk, aktivitet og sekresjon av cysteinproteasen legumain studert i ulike cellemodeller.
• Hemati, Paya Diana; Bosnjak, Tatjana; Nilsen, Hilde; Lunde, Ngoc Nguyen Dieu; Johansen, Harald Thidemann & Solberg, Rigmor (2017). The Proton Pump Inhibitor Lansoprazole Inhibits Protease Activity of Legumain.
• Røsjø, Bjarne & Solberg, Rigmor (2016). Desillusjonert over dopingbruken i idretten. [Internett]. titan.uio.no.
• Lunde, Ngoc Nguyen Dieu; Dahl, Tuva Børresdatter; Abdukadir, Nuriddin; Halvorsen, Bente; Solberg, Rigmor & Johansen, Harald Thidemann (2016). Increased secretion of legumain from pro-inflammatory M1 compared to M2 macrophages .
• Abdukadir, Nuriddin; Lunde, Ngoc Nguyen Dieu; Nilsen, Hilde; Solberg, Rigmor & Johansen, Harald Thidemann (2016). Regulering av cysteinproteaser ved differensiering av monocytter til makrofager.
• Larsen, Kristina Broe Bodin; Johansen, Harald Thidemann; Solberg, Rigmor & Lunde, Ngoc Nguyen Dieu (2016). Betydning av glykosylering for internalisering og aktivering av prolegumain i humane tykktarmskreftceller.
• Solberg, Rigmor; Rut, Wioletta; Lunde, Ngoc Nguyen Dieu; Kasperkiewicz, Paulina; Snipas, Scott J. & Mihelic, Marko [Vis alle 11 forfattere av denne artikkelen] (2016). New Selective Probes to Inhibit and Image Legumain in Living Cells.
• Solberg, Rigmor & Johansen, Harald Thidemann (2016). Involvement of the cysteine protease legumain in human health and disease.
• Johansen, Harald Thidemann; Elyouncha, Inass; Lunde, Ngoc Nguyen Dieu; Williams, Rich; Solberg, Rigmor & Nilsen, Hilde [Vis alle 7 forfattere av denne artikkelen] (2015). Opposing effects of glucose on legumain and cysteine cathepsins .
• Solberg, Rigmor; Poreba, Marcin; Rut, Wioletta; Kasperkiewicz, Paulina; Snipas, Scott & Turk, Boris [Vis alle 8 forfattere av denne artikkelen] (2015). Novel legumain-specific activity based probes binds and inhibits legumain in living cells.
• Lunde, Ngoc Nguyen Dieu; Nilsen, Hilde; Damgaard, Ingrid; Kasem, Roya; Solberg, Rigmor & Haugen, Mads Haugland [Vis alle 7 forfattere av denne artikkelen] (2015). Importance of glycosylation for legumain and cystatin E/M functions.
• Solberg, Rigmor (2015). Novel legumain specific cell-permeable activity based probes.
• Berven, Lise; Solberg, Rigmor & Samuelsen, Anne Berit C. (2014). Effects of alginates on legumain Activity in RAW 264.7 cells and on prolegumain autoactivation. Planta Medica. ISSN 0032-0943. 80(16), s. 1358–1358. doi: 10.1055/s-0034-1394502.
• Smith, Robert; Johansen, Harald Thidemann; Jacobsen, Linn Løkken; Voreland, Anette Larsen; Rustan, Arild & Thoresen, G. Hege [Vis alle 7 forfattere av denne artikkelen] (2013). Simvastatin inhibits legumain activity and processing in human myotubes.
• Haugen, Mads Haugland; Flatmark, Kjersti; Tamhane, Tripti; Boye, Kjetil; Pettersen, Solveig & Solberg, Rigmor [Vis alle 9 forfattere av denne artikkelen] (2013). Nuclear localized legumain in colorectal cancer.
• Smith, Robert; Johansen, Harald Thidemann; Nilsen, Hilde & Solberg, Rigmor (2013). Effects and interplay of legumain and cystatin E/M on migration and invasion of macrophages.
• Johansen, Harald Thidemann; Solberg, Rigmor; Nilsen, Hilde & Smith, Robert (2013). Effects and interplay of legumain and cystatin E/M om migration and invasion of macrophages.
• Tina, Elvestrand; Åstrand, Ove Alexander; Smith, Robert; Rongved, Pål; Nilsen, Hilde & Solberg, Rigmor [Vis alle 7 forfattere av denne artikkelen] (2013). Cellular effects of a colchicine-prodrug cleaved by legumain.
• Voreland, Anette; Smith, Robert; Thoresen, G. Hege; Johansen, Harald Thidemann & Solberg, Rigmor (2013). The cysteine protease legumain is downregulated by simvastatin in primary human skeletal muscle cells.
• Ånonsen, Kjersti Bergh; Nilsen, Hilde; Smith, Robert; Johansen, Harald Thidemann & Solberg, Rigmor (2013). Regulering av legumain i samspillet mellom makrofager og kreftceller.
• Berven, Lise; Johansen, Harald Thidemann; Solberg, Rigmor; Kolset, Svein Olav & Samuelsen, Anne Berit C. (2012). INTERACTIONS BETWEEN PROLEGUMAIN AND GLYCOSAMINOGLYCANS.
• Smith, Robert; Johansen, Harald Thidemann; Nilsen, Hilde; Yassen, Islam M.; Haugen, Mads Haugland & Pettersen, Solveig [Vis alle 9 forfattere av denne artikkelen] (2012). SECRETION, INTERNALIZATION AND INTERPLAY OF LEGUMAIN AND CYSTATIN E/M.
• Jacobsen, Linn Løkken; Smith, Robert; Thoresen, G. Hege; Solberg, Rigmor & Johansen, Harald Thidemann (2012). Are the cysteine proteases legumain and cathepsins involved in statin-induced myotoxicity?
• Tran, Anny T.; Smith, Robert; Solberg, Rigmor & Johansen, Harald Thidemann (2012). Effects of atorvastatin on regulation of protease activities in macrophages.
• Haugen, Mads Haugland; Mælandsmo, Gunhild; Johansen, Harald Thidemann; Solberg, Rigmor; Pettersen, Solveig & Boye, Kjetil [Vis alle 7 forfattere av denne artikkelen] (2011). Nuclear activity of the cysteine protease legumain in colorectal carcinoma.
• Smith, Robert; Johansen, Harald Thidemann; Nilsen, Hilde; Yassen, Islam M.; Haugen, Mads Haugland & Pettersen, Solveig J. [Vis alle 7 forfattere av denne artikkelen] (2011). SUBCELLULAR LOCALIZATION, INTERPLAY AND SECRETION OF LEGUMAIN AND CYSTATIN E/M IN HEK 293 CELLS.
• Johansen, Harald Thidemann; Smith, Robert; Tewolde, Eyassu; Nilsen, Hilde & Solberg, Rigmor (2011). ATORVASTATIN INHIBITS LEGUMAIN ACTIVITY IN AND PROLEGUMAIN SECRETION FROM HUMAN ACTIVATED MACROPHAGES.
• Smith, Robert; Johansen, Harald Thidemann & Solberg, Rigmor (2011). Cellular localization and interplay between legumain and its endogenous inhibitor cystatin E/M.
• Haugen, Mads Haugland; Johansen, Harald Thidemann; Solberg, Rigmor; Flatmark, Kjersti & Mælandsmo, Gunhild M (2009). Expression and activity of the cysteine protease legumain in colorectal carcinoma cell lines.
• Briggs, Jon; Haugen, Mads Haugland; Johansen, Harald Thidemann; Riker, Adam I; Abrahamson, Magnus & Fodstad, Øystein [Vis alle 8 forfattere av denne artikkelen] (2009). Cystatin E/M suppresses legumain activity and invasion of human melanoma.
• Solberg, Rigmor; Almlöf, Maria; Nilsen, Hilde; Ali, Zana Abdullrahman; Abrahamson, Magnus & Johansen, Harald Thidemann (2009). Asparaginyl endopeptidase activity is upregulated during differentiation of monocytes to macrophages but only partly mediated by legumain.
• Ben Omar, Sakina; Johansen, Harald Thidemann; Aukrust, Pål; Halvorsen, Bente & Solberg, Rigmor (2008). Lysosomal cysteine proteases in atherosclerosis: Do inflammatory modulators regulate expression and activity?
• Almlöf, Maria; Solberg, Rigmor & Johansen, Harald Thidemann (2007). Regulation of cystein proteases in monocytes/macrophages and in tumorigenesis.
• Solberg, Rigmor; Nilsen, Hilde; Johansen, Harald Thidemann; Mælandsmo, Gunhild M. & Briggs, Jon (2007). SCREENING OF THE EXPRESSIONS OF LEGUMAIN AND ITS SPECIFIC INHIBITOR CYSTATIN M IN VARIOUS MELANOMA CELLS.
• Almlöf, Maria; Solberg, Rigmor; Nilsen, Hilde & Johansen, Harald Thidemann (2006). Legumain expression and activity is highly increased as monocytes differentiate toward macrophages.
• Almlöf, Maria; Elenjord, Renate; Solberg, Rigmor; Winberg, Jan-Olof; Loennechen, Thrina & Johansen, Harald Thidemann (2006). Malignant osteosarcoma cells express higher levels of legumain compared to non-malignant cells.
• Almlöf, Maria; Elenjord, Renate; Solberg, Rigmor; Winberg, Jan Olof; Loennechen, Thrina & Johansen, Harald Thidemann (2006). The expression and activity of legumain is highly increased in malignant osteosarcoma cells compared to non-malignant cells.
• Solberg, Rigmor (2005). FRM 2410 - Formulering og bruk av legemidler. Norges apotekerforenings tidsskrift. ISSN 0802-8400. 113(2), s. 104–105.
• Brekke, Stian; Rønning, Camilla; Värn, Christine; Aas, Vigdis; Thoresen, G. Hege & Solberg, Rigmor (2005). Moxonidine exhibits direct effects on human skeletal muscle cells.
• Värn, Christine; Aas, Vigdis; Endresen, Marit JR & Solberg, Rigmor (2004). Moxonidine enhances glucose uptake in human skeletal muscle cells.
• Barsett, Hilde & Solberg, Rigmor (2004). New curriculum for master of pharmacy, School of Pharmacy, University of Oslo, Norway.
• Yaqub, Sheraz; Solhaug, Vigdis; Vang, Torkel; Solberg, Rigmor; Aasen, Ansgar Oddne & Tasken, Kjetil [Vis alle 7 forfattere av denne artikkelen] (2002). A Human Whole Blood Model Of LPS-Mediated Suppresion Of T-Cell Activation.
• Rustan, Arild; Solberg, Rigmor; Reseland, Janne Elin; Andersen, Merethe H; Drevon, Christian A & Aas, Vigdis (2002). FATTY ACIDS MODULATE LEPTIN AND LEPTIN RECEPTOR (OB-RB) GENE EXPRESSION AND LEPTIN SECRETION IN CULTURED HUMAN SKELETAL MUSCLE CELLS. Vis sammendrag

  Leptin is a hormone primarily secreted by adipocytes that plays a pivotal role in regulating food intake, energy expenditure and neuroendocrine function. Leptin stimulates oxidation of fatty acids and uptake of glucose, and prevents accumulation of lipids in nonadipose tissues. Inducible leptin expression in skeletal muscle cells (L6 rat cells) in response to insulin and glucosamine has been reported (Wang et al., Nature 1998, 393: 684-8). Based on this observation, we examined if leptin is present in skeletal muscle cells from human biopsies, and also if leptin and its receptor (OB-RB) could be modulated by hormones, fatty acids and other energy substrates. Leptin was expressed in differentiated myotubes, and both expression (mRNA) and secretion were changed after incubation with 0.1-0.6 mM of fatty acids for 24 and 48 h. Oleate (OA) and eicosapentaenoic acid (EPA 20:5 n-3) increased leptin secretion to the culture medium, with the strongest effect of OA after 48 h incubation. We also observed that incubation with palmitate (PA), OA and EPA for 24 and 48 h increased leptin mRNA expression, whereas the leptin receptor (OB-RB) mRNA expression was reduced 40-50 % by EPA. Moreover, the effect of these fatty acids on basal and insulin-stimulated glucose metabolism was also examined. Preincubation with PA and OA (0.6 mM for 24 h) induced insulin resistance assessed by decreased insulin-stimulated 2-deoxy-glucose transport, when compared to fatty acid-free controls. EPA on the other hand, did not reduce insulin-stimulated glucose transport, and caused a 2-fold increase in basal as well as insulin-stimulated glucose transport. We have for the first time demonstrated leptin expression in human skeletal muscle cells. Furthermore, this is the first documentation of regulation of OB-RB in any tissue examined. The physiological effect of fatty acids on the leptin axis in muscle cells needs further studies. We focus on how fatty acids affect leptin, OB-RB and their signalling pathways in glucose and lipid metabolism.

• Wang, Jacob Edward; Warris, A.; Ellingsen, Espen Alme; Jørgensen, Pål Foyn; Flo, T. H. & Espevik, T [Vis alle 9 forfattere av denne artikkelen] (2001). Involvement of CD 14 and toll-like receptors in signaling by Aspergillus hypae.
• Samuelsen, Anne Berit C.; Berven, Lise; Solberg, Rigmor; Johansen, Harald Thidemann & Truong, Hong Hoa Thi (2012). Effekt av alginat på legumain, en protease involvert i kreftutvikling. Universitetet i Oslo.
• Samuelsen, Anne Berit C.; Berven, Lise; Solberg, Rigmor; Johansen, Harald Thidemann & Nguyen, Nga Thi (2011). Studier av alginats effekt på prolegumain og cellesekresjon av matriksmetalloproteaser. Universitetet i Bergen.

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