Losartan inhibits LPS-induced inflammatory signaling through a PPARγ-dependent mechanism in human THP-1 macrophages

Jianbo An, Toshiaki Nakajima, Keiji Kuba, Akinori Kimura

Research output: Contribution to journalArticlepeer-review

50 Citations (Scopus)

Abstract

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-α, 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 IB phosphorylation, which is downstream of Toll-like receptor activation. Peroxisome proliferator-activated receptor-gamma (PPARγ) antagonists, GW9662 and T0070907, reversed the inhibitory effects of losartan on LPS-induced TNF-α and IL-8 expression in THP-1 macrophages. These observations suggest that losartan inhibits LPS-induced proinflammatory gene expression in macrophages by activating the PPARγ pathway rather than by the competitive inhibition of AT1R binding to AngII.

Original languageEnglish
Pages (from-to)831-835
Number of pages5
JournalHypertension Research
Volume33
Issue number8
DOIs
Publication statusPublished - Aug 2010
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Internal Medicine
  • Physiology
  • Cardiology and Cardiovascular Medicine

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