Inhibition of tumor necrosis factor-α-induced interleukin-6 expression by Telmisartan through cross-talk of peroxisome proliferator- activated receptor-γ with nuclear factor κB and CCAAT/Enhancer- Binding protein-β

Qingping Tian, Ryohei Miyazaki, Toshihiro Ichiki, Ikuyo Imayama, Keita Inanaga, Hideki Ohtsubo, Kotaro Yano, Kotaro Takeda, Kenji Sunagawa

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43 Citations (Scopus)

Abstract

Telmisartan, an angiotensin II type 1 receptor antagonist, was reported to be a partial agonist of peroxisome proliferator-activated receptor-γ. Although peroxisome proliferator-activated receptor-γ activators have been shown to have an anti-inflammatory effect, such as inhibition of cytokine production, it has not been determined whether telmisartan has such effects. We examined whether telmisartan inhibits expression of interleukin-6 (IL-6), a proinflammatory cytokine, in vascular smooth muscle cells. Telmisartan, but not valsartan, attenuated IL-6 mRNA expression induced by tumor necrosis factor-α (TNF-α). Telmisartan decreased TNF-α-induced IL-6 mRNA and protein expression in a dose-dependent manner. Because suppression of IL-6 mRNA expression was prevented by pretreatment with GW9662, a specific peroxisome proliferator-activated receptor-7 antagonist, peroxisome proliferatoractivated receptor-γ may be involved in the process. Telmisartan suppressed IL-6 gene promoter activity induced by TNF-α. Deletion analysis suggested that the DNA segment between -150 bp and -27 bp of the IL-6 gene promoter that contains nuclear factor κB and CCAAT/enhancer-binding protein-β sites was responsible for telmisartan suppression. Telmisartan attenuated TNF-α-induced nuclear factor κB- and CCAAT/enhancer-binding protein-βdependent gene transcription and DNA binding. Telmisartan also attenuated serum IL-6 level in TNF-α-infused mice and IL-6 production from rat aorta stimulated with TNF-α ex vivo. These data suggest that telmisartan may attenuate inflammatory process induced by TNF-α in addition to the blockade of angiotensin II type 1 receptor. Because both TNF-α and angiotensin II play important roles in atherogenesis through enhancement of vascular inflammation, telmisartan may be beneficial for treatment of not only hypertension but also vascular inflammatory change.

Original languageEnglish
Pages (from-to)798-804
Number of pages7
JournalHypertension
Volume53
Issue number5
DOIs
Publication statusPublished - May 1 2009

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All Science Journal Classification (ASJC) codes

  • Internal Medicine

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