Scavenger receptor SRECI can bind to Toll like receptor 4 and activate LPS-mediated signaling (P1362)

Abstract

Abstract Transmembrane receptor TLR4 was shown to induce the inflammatory response in the presence of its ligand, LPS. All TLRs belong to a family of PRR (pattern recognition receptor) which recognize PAMPs (pathogen-associated molecular patterns). The other receptor families, scavenger receptors work along with TLRs to attenuate innate immunity. SREC-I is a scavenger receptor expressed by immune cells and has a role in CD8+ T cell immunity. SREC-I can also modulate the function of Toll like receptors which have essential roles in innate immunity. Here we show that SREC-I can activate LPS mediated NFkB signaling. SREC-I can bind to TLR4 in the presence of LPS. We found that human monocyte/macrophage THP1 cells as well as bone marrow derived macrophages from mice exhibited increased responses to LPS and enhanced production of inflammatory cytokines such as IL-8, IL-6 with overexpressed SREC-I. We were able to show that downstream activation of NFkB requires either MyD88 or Trif adaptor protein. Our data suggested that SRECI is a cell surface receptor capable of internalizing LPS along with TLR4 as well as activating TLR4 mediated downstream cytokine production in macrophages.