Autocrine-paracrine prostaglandin E₂ signaling restricts TLR4 internalization and TRIF signaling.

ABSTRACT: The unique cell biology of Toll-like receptor 4 (TLR4) allows it to initiate two signal-transduction cascades: a signal dependent on the adaptors TIRAP (Mal) and MyD88 that begins at the cell surface and regulates proinflammatory cytokines, and a signal dependent on the adaptors TRAM and TRIF that begins in the endosomes and drives the production of type I interferons. Negative feedback circuits to limit TLR4 signals from both locations are necessary to balance the inflammatory response. We describe a negative feedback loop driven by autocrine-paracrine prostaglandin E₂ (PGE₂) and the PGE₂ receptor EP4 that restricted TRIF-dependent signals and the induction of interferon-β through the regulation of TLR4 trafficking. Inhibition of PGE₂ production

SUBMITTER: Perkins DJ 

PROVIDER: S-EPMC6240378 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature