研究業績

OBJECTIVE: Resistin-like molecule (RELM) beta is a secretory protein homologous to resistin and reportedly contributes to local immune response regulation in gut and bronchial epithelial cells. However, we found that activated macrophages also express RELMbeta and thus investigated the role of RELMbeta in the development of atherosclerosis. APPROACH AND RESULTS: It was demonstrated that foam cells in atherosclerotic lesions of the human coronary artery abundantly express RELMbeta. RELMbeta knockout ((-/-)) and wild-type mice were mated with apolipoprotein E-deficient background mice. RELMbeta(-/-) apolipoprotein E-deficient mice exhibited less lipid accumulation in the aortic root and wall than RELMbeta(+/+) apolipoprotein E-deficient mice, without significant changes in serum lipid parameters. In vitro, RELMbeta(-/-) primary cultured peritoneal macrophages (PCPMs) exhibited weaker lipopolysaccharide-induced nuclear factor-kappaB classical pathway activation and inflammatory cytokine secretion than RELMbeta(+/+), whereas stimulation with RELMbeta upregulated inflammatory cytokine expressions and increased expressions of many lipid transporters and scavenger receptors in PCPMs. Flow cytometric analysis revealed inflammatory stimulation-induced RELMbeta in F4/80(+) CD11c(+) PCPMs. In contrast, the expressions of CD11c and tumor necrosis factor were lower in RELMbeta(-/-) PCPMs, but both were restored by stimulation with recombinant RELMbeta. CONCLUSIONS: RELMbeta is abundantly expressed in foam cells within plaques and contributes to atherosclerosis development via lipid accumulation and inflammatory facilitation.