title: Macrophage SR-BI regulates LPS-induced pro-inflammatory signaling in mice and isolated macrophages.
abstract: Scavenger receptor BI (SR-BI), an HDL receptor, plays a key role in reverse cholesterol transport. In mice, disruption of SR-BI results in hypersensitivity to lipopolysaccharide (LPS) and bacteria-induced septic shock due to adrenal insufficiency and abnormal hepatic pathogen clearance. In this study, we identify an anti-inflammatory role of macrophage SR-BI. Using bone marrow transplantation, we report an enhanced pro-inflammatory response to LPS in wild-type (WT) mice receiving SR-BI-null compared with WT bone marrow cells and a reduced response in SR-BI-null mice receiving WT compared with SR-BI-null cells. Although significant, SR-BI deficiency limited to bone marrow-derived cells promoted a relatively modest enhancement of the inflammatory response to LPS in mice compared with the effect of whole-body SR-BI deletion. Consistent with earlier findings, SR-BI-null primary macrophages exhibited a greater inflammatory cytokine response to LPS than control macro phages. In addition, we showed that overexpression of SR-BI in J774 macrophages attenuated the inflammatory response to LPS. The LPS-induced cytokine expression in both WT and SR-BI-null macrophages was dependent not only on NFκB as previously reported but also on JNK and P38 cell signaling pathways. The increased inflammatory signaling in SR-BI-null cells was not related to alterations in cellular cholesterol content. We conclude that SR-BI plays an important function in regulating the macrophage inflammatory response to LPS.
authors.affiliation: Department of Veterans Affairs Medical Center, Lexington, KY, USA.
authors.forename: Lei
authors.initials: L
authors.lastname: Cai
authors.forename: Zhen
authors.initials: Z
authors.lastname: Wang
authors.forename: Jason M
authors.initials: JM
authors.lastname: Meyer
authors.forename: Ailing
authors.initials: A
authors.lastname: Ji
authors.forename: Deneys R
authors.initials: DR
authors.lastname: van der Westhuyzen
mesh_terms: D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D016026:Bone Marrow Transplantation; D018955:CD36 Antigens / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D002469:Cell Separation; D002784:Cholesterol / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D017353:Gene Deletion; D005786:Gene Expression Regulation / Q000187:drug effects; D007249:Inflammation / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D008070:Lipopolysaccharides / Q000378:metabolism / Q000494:pharmacology*; D008264:Macrophages / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D018955:CD36 Antigens; D016207:Cytokines; D008070:Lipopolysaccharides; D016328:NF-kappa B; D002784:Cholesterol; D048031:JNK Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases