Serum-borne lipids amplify TLR-activated inflammatory responses - PubMed (original) (raw)
. 2021 Apr;109(4):821-831.
doi: 10.1002/JLB.3AB0720-241RR. Epub 2020 Jul 27.
Affiliations
- PMID: 32717772
- DOI: 10.1002/JLB.3AB0720-241RR
Serum-borne lipids amplify TLR-activated inflammatory responses
Naveen Sharma et al. J Leukoc Biol. 2021 Apr.
Abstract
TLRs recognize conserved pathogen associated molecular patterns and generate innate immune responses. Several circulating and cell membrane associated proteins have been shown to collaborate with TLRs in sensing microbial ligands and promoting inflammatory responses. Here, we show that serum and serum-borne lipids including lysophosphatidylcholine (LPC) amplify inflammatory responses from intestinal epithelial cells and mononuclear phagocytes primed with microbial TLR ligands. Treatment with the inhibitors of G protein-coupled receptor (GPCR) signaling, suramin, or pertussis toxin (PT), the inhibitor of JNK-MAPK, or knockdown of LPC response-regulating GPCR, G2A, decreases the augmentation brought about by serum or LPC in TLR-induced inflammatory response. In vivo administration of PT or anti-G2A antibody reduces TLR2-activated cytokine secretion. The ability of host lipids to costimulate TLR-generated cellular responses represents a novel pathway for the amplification of innate immunity and inflammation.
Keywords: G protein-coupled receptor; TLR; lysophosphatidylcholine; serum-borne lipids.
©2020 Society for Leukocyte Biology.
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