Treatment with Anti-HMGB1 Monoclonal Antibody Does Not Affect Lupus Nephritis in MRL/lpr Mice
| Autor: | Pieter C. Limburg, Marc Bijl, Arjen H. Petersen, Johanna Westra, Gerda Horst, Peter Heeringa, Mirjan M. van Timmeren, Fleur Schaper |
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| Přispěvatelé: | Translational Immunology Groningen (TRIGR), Groningen Kidney Center (GKC), Groningen Institute for Organ Transplantation (GIOT) |
| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
medicine.drug_class ERYTHEMATOSUS Lupus nephritis chemical and pharmacologic phenomena HMGB1 Monoclonal antibody DISEASE Proinflammatory cytokine ACTIVATION lcsh:Biochemistry 03 medical and health sciences CYTOKINE RELEASE GLOMERULONEPHRITIS immune system diseases Genetics medicine lcsh:QD415-436 Neutralizing antibody skin and connective tissue diseases Molecular Biology Genetics (clinical) MOBILITY GROUP BOX-1 biology business.industry lcsh:RM1-950 Glomerulonephritis medicine.disease SEPSIS SURVIVORS 030104 developmental biology lcsh:Therapeutics. Pharmacology Immunology Monoclonal biology.protein CHROMOSOMAL-PROTEIN 1 Molecular Medicine Antibody ARTHRITIS business Research Article |
| Zdroj: | Molecular Medicine, Vol 22, Iss 1, Pp 12-21 (2016) Molecular medicine, 22, 12-21. FEINSTEIN INST MED RES |
| ISSN: | 1076-1551 |
| Popis: | High mobility group box 1 (HMGB1) is a nuclear DNA binding protein that acts as an alarmin when secreted. HMGB1 is increased in systemic lupus erythematosus and might represent a potential therapeutic target. We investigated whether treatment with an anti-HMGB1 antibody affects the development of lupus nephritis in MRL/lpr mice. Seven-week-old MRL/lpr mice were injected intraperitoneally twice weekly for 10 wks with 50 µg monoclonal anti-HMGB1 (2G7, mouse IgG2b) (n = 12) or control antibody (n = 11). Control MRL/MPJ mice (n = 10) were left untreated. Every 2 wks, blood was drawn and urine was collected at wk 7, 11 and 17. Mice were sacrificed at 17 wks for complete disease evaluation. Plasma HMGB1 and anti-HMGB1 levels were increased in MRL/lpr mice compared with control MRL/MPJ mice. There were no differences in albuminuria, urine HMGB1 and plasma levels of complement C3, anti-dsDNA and proinflammatory cytokines between untreated and treated mice at any time point. Lupus nephritis of mice treated with anti-HMGB1 monoclonal antibody (mAb) was classified as class III (n = 3) and class IV (n = 9), while mice treated with control mAb were classified as class II (n = 4), class III (n = 2) and class IV (n = 5). IgG and C3 deposits in kidneys were similar in mice treated with anti-HMGB1 mAb or control mAb. In conclusion, treatment with monoclonal anti-HMGB-1 antibody 2G7 does not affect development of lupus nephritis, disease progression or proinflammatory cytokine levels in MRL/lpr mice. This result indicates that blocking of HMGB1 by this neutralizing antibody does not affect lupus nephritis in MRL/lpr mice. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
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