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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Woodruff, T. M. Stadnyk, A. W. Jain, U. |
| Description | Author Affiliation: Jain U ( Department of Microbiology and Immunology, Dalhousie University, Halifax, NS, Canada.) |
| Abstract | BACKGROUND AND PURPOSE: Anti-complement therapies have not been advanced for treating the inflammatory bowel diseases (IBDs) despite a growing body of evidence that blocking C5a protects against induced colitis in rodents. The purpose of this study was to further build on this evidence by examining the efficacy, mechanism and specificity of a potent, non-competitive and orally active C5a receptor (CD88) antagonist, PMX205, in the dextran sulphate sodium (DSS) model of murine innate colitis. EXPERIMENTAL APPROACH: Mice with DSS added to their drinking water were orally administered 100 or 200 µg day(-1) PMX205 in prophylactic and therapeutic regimens. Clinical illness, colon histology and local generation of inflammatory mediators were measured to evaluate the impact of PMX205 on disease. KEY RESULTS: PMX205 significantly prevented DSS-induced colon inflammation in both regimens, associated with lower pro-inflammatory cytokine production and nitrotyrosine staining in colon sections. Additionally, the levels of anti-inflammatory cytokines IL-4 and IL-10 were increased. PMX205 had no significant effect on C5a levels. The beneficial effect of PMX205 was seen in two strains of mice of differing sensitivities to DSS inflammation, but was inactive in mice lacking CD88. CONCLUSIONS AND IMPLICATIONS: Pharmacological inhibition of C5a activity by PMX205 is efficacious in preventing DSS-induced colitis, providing further evidence that targeting CD88 in IBD patients could be a valuable therapeutic option. |
| ISSN | 00071188 |
| e-ISSN | 14765381 |
| Journal | British Journal of Pharmacology |
| Issue Number | 2 |
| Volume Number | 168 |
| Language | English |
| Publisher | Wiley Online Library(on behalf of The British Pharmacological Society) |
| Publisher Date | 2013-01-01 |
| Publisher Place | Great Britain (UK) |
| Access Restriction | Open |
| Subject Keyword | Anti-Inflammatory Agents Therapeutic Use Colitis Drug Therapy Peptides, Cyclic Receptor, Anaphylatoxin C5a Antagonists & Inhibitors Animals Pharmacology Chemically Induced Immunology Pathology Complement C3a Complement C5a Cytokines Dextran Sulfate Mice Mice, Inbred BALB C Mice, Inbred C57BL Mice, Knockout Genetics Research Support, Non-U.S. Gov't |
| Content Type | Text |
| Resource Type | Article |
| Subject | Pharmacology |
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