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Major vault protein regulates class A scavenger receptor-mediated tumor necrosis factor-α synthesis and apoptosis in macrophages.
|Title||Major vault protein regulates class A scavenger receptor-mediated tumor necrosis factor-α synthesis and apoptosis in macrophages.|
|Publication Type||Journal Article|
|Year of Publication||2013|
|Authors||Ben J, Zhang Y, Zhou R, Zhang H, Zhu X, Li X, Zhang H, Li N, Zhou X, Bai H, Yang Q, Li D, Xu Y, Chen Q|
|Journal||The Journal of biological chemistry|
|Date Published||2013 Jul 5|
Atherosclerosis is considered a disease of chronic inflammation largely initiated and perpetuated by macrophage-dependent synthesis and release of pro-inflammatory mediators. Class A scavenger receptor (SR-A) expressed on macrophages plays a key role in this process. However, how SR-A-mediated pro-inflammatory response is modulated in macrophages remains ill defined. Here through immunoprecipitation coupled with mass spectrometry, we reported major vault protein (MVP) as a novel binding partner for SR-A. The interaction between SR-A and MVP was confirmed by immunofluorescence staining and chemical cross-linking assay. Treatment of macrophages with fucoidan, a SR-A ligand, led to a marked increase in TNF-α production, which was attenuated by MVP depletion. Further analysis revealed that SR-A stimulated TNF-α synthesis in macrophages via the caveolin- instead of clathrin-mediated endocytic pathway linked to p38 and JNK, but not ERK, signaling pathways. Importantly, fucoidan invoked an enrichment of MVP in lipid raft, a caveolin-reliant membrane structure, and enhanced the interaction among SR-A, caveolin, and MVP. Finally, we demonstrated that MVP elimination ameliorated SR-A-mediated apoptosis in macrophages. As such, MVP may fine-tune SR-A activity in macrophages which contributes to the development of atherosclerosis.
|Alternate Journal||J. Biol. Chem.|