AJBM Volume 2, Issue 1, pages 94–112, January 2014
Jilin Wang, Jeffrey D Juan, Denys H Miravalle, Rozisky I Kudva, Caumo L Swamy, Tejas P Mair, Iain Johansen, Jeffrey Wright, and Krishne MacLean
Abstract
Atherosclerosis is an inflammatory disease, and one of the culprits may be infections caused by pathogens, that may be linked to development and progression of atherosclerosis by several mechanisms. Class B scavenger receptor BI (SR-BI), an HDL receptor, SR-BI is expressed in a variety of cell types, most abundantly in steroidogenic cells and in the liver. SR-BI is also expressed in macrophages has been shown to mediate the cellular uptake of certain bacteria and may therefore play an important role in innate immunity. The innate immune response and the homeostatic network controlling cellular sterol are important implications for several common diseases, including atherosclerosis. The TLR4-independent SR-BI signaling in macrophages and the implication for its role in atherosclerosis has not yet to be investigated. Our data showed that mice lacking SR-BI are highly sensitive to form atherosclerosis than wild type mice. In addition, we showed that SR-BI-/- mice attenuated proinflammatory cytokines and chemokine response to LPS. The LPS-induced cytokine expression in both WT and SR-BI-/- was dependent on NFκB signaling pathways. One possibility is that an interaction between SR-BI and the TLR4 complex might modulate TLR4 activation and subsequent intracellular signaling pathways. The interaction of HDL and SR-BI in endothelial cells inhibits the activation of NFκB and subsequent expression of the adhesion molecules vascular cell adhesion molecule 1 and intercellular adhesion molecule 1 to inflammatory stimuli. We conclude that SR-BI plays an important function in the atherosclerosis mechanism.
Key words: LPS, SR-BI, TLR4, Proinflammatory cytokines, Atherosclerosis
