Gain-of-Function Mutation of Tristetraprolin Impairs Negative Feedback Control of Macrophages In Vitro yet Has Overwhelmingly Anti-Inflammatory Consequences In Vivo.

摘要: The mRNA-destabilizing factor tristetraprolin (TTP) binds in a sequence-specific manner to the 3' untranslated regions of many proinflammatory mRNAs and recruits complexes nucleases promote rapid mRNA turnover. Mice lacking TTP develop severe, spontaneous inflammatory syndrome characterized by overexpression tumor necrosis other mediators. However, also employs same mechanism inhibit expression potent anti-inflammatory cytokine interleukin 10 (IL-10). Perturbation function may therefore have mixed effects on responses, either increasing or decreasing factors via direct indirect mechanisms. We recently described knock-in mouse strain which substitution 2 amino acids endogenous protein renders it constitutively active as an factor. Here we investigate impact IL-10-mediated response. It is shown that gain-of-function mutation impairs negative feedback control macrophage vitro vivo are uniformly despite decreased IL-10.