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

ABSTRACT: The mRNA-destabilizing factor tristetraprolin (TTP) binds in a sequence-specific manner to the 3' untranslated regions of many proinflammatory mRNAs and recruits complexes of nucleases to promote rapid mRNA turnover. Mice lacking TTP develop a severe, spontaneous inflammatory syndrome characterized by the overexpression of tumor necrosis factor and other inflammatory mediators. However, TTP also employs the same mechanism to inhibit the expression of the potent anti-inflammatory cytokine interleukin 10 (IL-10). Perturbation of TTP function may therefore have mixed effects on inflammatory responses, either increasing or decreasing the expression of proinflammatory factors via direct or indirect mechanisms. We recently described a knock-in mouse strain in which the substitution of 2 amino ac

SUBMITTER: O'Neil JD 

PROVIDER: S-EPMC5440651 | biostudies-literature | 2017 Jun

REPOSITORIES: biostudies-literature