| First Author | Criado G | Year | 2014 |
| Journal | Arthritis Rheumatol | Volume | 66 |
| Issue | 5 | Pages | 1208-17 |
| PubMed ID | 24782184 | Mgi Jnum | J:301851 |
| Mgi Id | MGI:6507239 | Doi | 10.1002/art.38327 |
| Citation | Criado G, et al. (2014) Alternative p38 MAPKs are essential for collagen-induced arthritis. Arthritis Rheumatol 66(5):1208-17 |
| abstractText | OBJECTIVE: The role of most p38 MAPK isoforms in inflammatory arthritis is not known. This study was undertaken to evaluate p38gamma and p38delta deficiency in the collagen-induced arthritis (CIA) model. METHODS: Wild-type, p38gamma(-/-) , p38delta(-/-) , and p38gamma/delta(-/-) mice were immunized with chicken type II collagen, and disease activity was evaluated by semiquantitative scoring and histologic assessment. Serum cytokine levels and in vitro T cell cytokine responses were quantified by flow cytometry and multiplex analysis, and serum anticollagen antibody levels by enzyme-linked immunosorbent assay. Cytokine and p38 MAPK isoform expression in joints were determined by quantitative polymerase chain reaction. RESULTS: Compound p38gamma and p38delta deficiency markedly reduced arthritis severity compared with that in wild-type mice, whereas lack of either p38gamma or p38delta had an intermediate effect. Joint damage was minimal in arthritic p38gamma/delta(-/-) mice compared with wild-type mice. The p38gamma/delta(-/-) mice had lower levels of pathogenic anticollagen antibodies and interleukin-1beta (IL-1beta) and tumor necrosis factor alpha than controls. In vitro T cell assays showed reduced proliferation, interferon-gamma (IFNgamma) production, and IL-17 production by lymph node cells from p38gamma/delta(-/-) mice. IL-17 and IFNgamma messenger RNA expression in joints was significantly inhibited in p38gamma/delta(-/-) mice. Wild-type chimeric mice with p38gamma/delta(-/-) bone marrow did not show decreased CIA. CONCLUSION: Reduced disease severity in p38gamma/delta(-/-) mice was associated with lower cytokine production and anticollagen antibody responses than in controls, indicating that p38gamma and p38delta are crucial regulators of inflammatory joint destruction in CIA. Our findings indicate that p38gamma and p38delta are potential therapeutic targets in complex diseases, such as rheumatoid arthritis, that involve innate and adaptive immune responses. |
