Macrophage SR-BI regulates LPS-induced pro-inflammatory signaling in mice and isolated macrophages

• Published in: Journal of lipid research 2012-08, Vol.53 (8), p.1472-1481
• Main Authors: Cai, Lei, Wang, Zhen, Meyer, Jason M., Ji, Ailing, van der Westhuyzen, Deneys R.
• Format: Article
• Language: English
• Subjects: Animals; Biological Transport - drug effects; Bone Marrow Transplantation; CD36 Antigens - deficiency; CD36 Antigens - genetics; CD36 Antigens - metabolism; Cell Separation; Cholesterol - metabolism; Cytokines - metabolism; Gene Deletion; Gene Expression Regulation - drug effects; inflammation; Inflammation - chemically induced; Inflammation - genetics; Inflammation - metabolism; Inflammation - pathology; JNK Mitogen-Activated Protein Kinases - metabolism; lipopolysaccharide; Lipopolysaccharides - metabolism; Lipopolysaccharides - pharmacology; Macrophages - cytology; Macrophages - drug effects; Macrophages - metabolism; Macrophages - pathology; Male; Mice; NF-kappa B - metabolism; p38 Mitogen-Activated Protein Kinases - metabolism; scavenger receptor; Signal Transduction - drug effects
• ISSN: 0022-2275; 1539-7262
• DOI: 10.1194/jlr.M023234

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.