Bimodal role of NADPH oxidases in the regulation of biglycan-triggered IL-1β synthesis.

ABSTRACT: Biglycan, a ubiquitous proteoglycan, acts as a danger signal when released from the extracellular matrix. As such, biglycan triggers the synthesis and maturation of interleukin-1β (IL-1β) in a Toll-like receptor (TLR) 2-, TLR4-, and reactive oxygen species (ROS)-dependent manner. Here, we discovered that biglycan autonomously regulates the balance in IL-1β production in vitro and in vivo by modulating expression, activity and stability of NADPH oxidase (NOX) 1, 2 and 4 enzymes via different TLR pathways. In primary murine macrophages, biglycan triggered NOX1/4-mediated ROS generation, thereby enhancing IL-1β expression. Surprisingly, biglycan inhibited IL-1β due to enhancement of NOX2 synthesis and activation, by selectively interacting with TLR4. Synthesis of NOX2 was mediated by adaptor

SUBMITTER: Hsieh LT 

PROVIDER: S-EPMC6953411 | biostudies-literature | 2016 Jan

REPOSITORIES: biostudies-literature