Anti-inflammatory roles of p38α MAPK in macrophages are context dependent and require IL-10.

ABSTRACT: The p38 MAPK pathway was originally identified as a master regulator of proinflammatory cytokine production by myeloid cells. Numerous drugs targeting this kinase showed promise in preclinical models of inflammatory disease, but so far, none have shown efficacy in clinical trials. The reasons behind this are unclear, but may, in part, be explained by emerging anti-inflammatory functions of this kinase or overly refined selectivity of second-generation pharmacologic inhibitors. Here, we show that p38α signaling in macrophages plays pro- and anti-inflammatory functions in vivo and in vitro, with the outcome depending on the stimulus, output, kinetics, or mode of kinase inhibition (genetic vs. pharmacologic). Different pharmacologic inhibitors of p38 exhibit opposing effects, with second-gene

SUBMITTER: Raza A 

PROVIDER: S-EPMC6608039 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature