MicroRNA-302b augments host defense to bacteria by regulating inflammatory responses via feedback to TLR/IRAK4 circuits.

ABSTRACT: MicroRNAs (miRNAs) have been implicated in a spectrum of physiological and pathological conditions, including immune responses. miR-302b has been implicated in stem cell differentiation but its role in immunity remains unknown. Here we show that miR-302b is induced by Toll-like receptor 2 (TLR2) and TLR4 through ERK-p38-NF-?B signalling upon Gram-negative bacterium Pseudomonas aeruginosa infection. Suppression of inflammatory responses to bacterial infection is mediated by targeting IRAK4, a protein required for the activation and nuclear translocation of NF-?B. Through negative feedback, enforced expression of miR-302b or IRAK4 siRNA silencing inhibits downstream NF-?B signalling and airway leukocyte infiltration, thereby alleviating lung injury and increasing survival in P. aeruginosa-infected mice. In contrast, miR-302b inhibitors exacerbate inflammatory responses and decrease survival in P. aeruginosa-infected mice and lung cells. These findings reveal that miR-302b is a novel inflammatory regulator of NF-?B activation in respiratory bacterial infections by providing negative feedback to TLRs-mediated immunity.

SUBMITTER: Zhou X 

PROVIDER: S-EPMC4011559 | biostudies-literature | 2014 Apr

REPOSITORIES: biostudies-literature