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.