Involvement of WSX-1 in atherosclerosis

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Atherosclerosis is a chronic inflammatory disease. It has been shown that cytokines play important roles in vascular inflammation in atherosclerosis. IL-27 that is a member of IL-12 family regulates Th1 cell differentiation and production of inflammatory cytokines from T cells. In this study, we aimed to examine the involvement of EBI3, a component of IL-27, and WSX-1, a component of IL-27 receptor, in atherosclerosis.We crossed EBI3 knockout mice and WSX-1 knockout mice with atherosclerosis-prone LDL receptor knockout mice to generate double knockout mice. LDL receptor knockout mice and double knockout mice were fed with high cholesterol diet for 16 weeks from the age of 8 weeks old. Body weight, blood pressure and serum cholesterol levels showed no significant differences among LDL receptor knockout mice and double knockout mice. Atherosclerotic lesions in aorta stained with oil red O were larger in double knockout mice than in LDL receptor knockout mice. Areas stained with MOMA-2, a macrophage marker, in atherosclerotic lesions were larger in double knockout mice than in LDL receptor knockout mice.These data suggest that deficiency of EBI3 and WSX-1 promotes atherosclerosis through macrophage activation. Further studies are necessary to elucidate the molecular mechanisms responsible for macrophage activation in deficiency of EBI3 and WSX-1.