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JAK1/STAT3 activation directly inhibits IL-12 production in dendritic cells by preventing CDK9/P-TEFb recruitment to the p35 promoter.
Abstract Inhibition of Janus-activated kinase-1 (JAK1) is a promising clinical concept for post-transplant immunosuppression and autoimmunity. However, it also raises concerns regarding possible immunosuppressive side effects. Our study investigates JAK1 signalling in the context of CD40L and bacterially activated human MoDC using siRNA and biological inhibitors. We demonstrate that strong stimuli (e.g. intact E. coli or LPS in addition to IL-1β) induce IL-12p70 via a ROS/RELA/CDK9 pathway that is inhibited by simultaneous JAK1/STAT3 signalling. Transcription is effective if RELA recruits the positive transcripti...
Source: Biochemical Pharmacology - April 27, 2015 Category: Drugs & Pharmacology Authors: Wagner AH, Conzelmann M, Fitzer F, Giese T, Gülow K, Falk CS, Krämer OH, Dietrich S, Hecker M, Luft T Tags: Biochem Pharmacol Source Type: research