Alternative p38 MAPKs Are Essential for Collagen-Induced Arthritis
MAPK family proteins are regulatory proteins, affecting processes such as synthesis and release of proinflammatory molecules which contribute to the pathogenesis of RA. In particular, the p38 MAPK protein family is central to proinflammatory cytokine production. There are four member of the p38 group; p38α, p38β, p38γ and p38δ. This study sought to evaluate p38γ and p38δ deficiency in mice CIA model.
In p38γ-/- or p38δ-/- mice, the percentage of mice with arthritis was lower than wild type but severity of disease were comparable across all three groups (C57BL/6 mice being the third group). However, p38γ/δ-null mice showed lower disease incidence and a decrease in clinical score when compared with the wild-type mice.
These data, plus the known crucial role of p38γ/δ in cytokine production, synovial inflammation and bone erosion, suggest that p38γ/δ could serve as a novel therapeutic and an alternative to traditional p38α inhibitors, which have proven minimally effective in human trials.