Candesartan inhibits Toll-like receptor expression and activity both in vitro and in vivo

Mohan R. Dasu, Andrea C. Riosvelasco, Ishwarlal Jialal

Research output: Contribution to journalArticle

59 Scopus citations

Abstract

Introduction: Toll-like receptors play an important role in the innate immune system and are found to be crucial in severe diseases like sepsis, atherosclerosis, and arthritis. TLR2 and TLR4 expression is upregulated in the inflammatory diseases. Angiotensin II in addition to stimulating vasoconstriction also induces an increase in ROS and a proinflammatory phenotype via AT1R. Angiotensin II type-1 receptor blocker (ARB), widely used as an antihypertensive drug, has been reported to also have anti-inflammatory effects. Thus, we investigated whether an ARB exerts anti-inflammatory effects via inhibiting TLR2 and TLR4 expression. Methods and results: Monocytes were isolated from healthy human volunteers and treated with the synthetic lipoprotein Pam3CSK4 or LPS in the absence or presence of candesartan. Pretreatment of human monocytes with candesartan significantly decreased Pam3CSK4 or LPS induced TLR2 and TLR4 expression of both mRNA and protein levels (P < 0.05 vs. control) along with decrease in the activity of NF-κB and the expression of IL-1β, IL-6, TNF-α, and MCP-1. Furthermore, candesartan treated mice show decreased TLR2 and TLR4 expression compared to vehicle control mice. Conclusion: Pam3CSK4 and LPS induced TLR2 and TLR4 expression at mRNA and protein levels are inhibited by candesartan both in vitro and in vivo. Thus, we define a novel pathway by which candesartan could induce anti-inflammatory effects.

Original languageEnglish (US)
Pages (from-to)76-83
Number of pages8
JournalAtherosclerosis
Volume202
Issue number1
DOIs
StatePublished - Jan 2009

Keywords

  • Angiotensin receptor blocker
  • Inflammation
  • LPS
  • Monocytes
  • Nuclear factor-kappa B
  • Toll-like receptors

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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