期刊
HYPERTENSION RESEARCH
卷 33, 期 8, 页码 831-835出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/hr.2010.79
关键词
inflammatory cytokine; losartan; LPS; macrophage; PPAR gamma
资金
- Ministry of Education, Culture, Sports, Science and Technology, Japan
- Japan Society for the Promotion of Science
- Founding Research Centers for Emerging and Reemerging Infectious Diseases
- Ministry of Health, Labour and Welfare, Japan
- Institute of Seizon and Life Sciences
Macrophages have critical roles in the pathogenesis of atherosclerosis by activating the innate immune system and producing inflammatory cytokines. Accumulating evidence indicates that angiotensin type 1 receptor (AT1R) blockers exert anti-inflammatory effects in inflammatory diseases including atherosclerosis. In this study, we investigated the effect of losartan, an AT1R blocker, on the proinflammatory gene expression induced by bacterial lipopolysaccharide (LPS) in a well-defined in vitro human THP-1 macrophage system. We found that losartan significantly attenuated the LPS-induced expression of proinflammatory genes TNF-alpha, IL-8 and COX-2. However, exogenous angiotensin II (AngII) had no effect on LPS-induced inflammatory signaling despite the expression of AT1R. In addition, losartan did not block LPS-induced I kappa B phosphorylation, which is downstream of Toll-like receptor activation. Peroxisome proliferator-activated receptor-gamma (PPAR gamma) antagonists, GW9662 and T0070907, reversed the inhibitory effects of losartan on LPS-induced TNF-alpha and IL-8 expression in THP-1 macrophages. These observations suggest that losartan inhibits LPS-induced proinflammatory gene expression in macrophages by activating the PPAR gamma pathway rather than by the competitive inhibition of AT1R binding to AngII. Hypertension Research (2010) 33, 831-835; doi: 10.1038/hr.2010.79; published online 27 May 2010
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