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Inhibition of Tumor Necrosis Factor-alpha-Induced Interleukin-6 Expression by Telmisartan Through Cross-Talk of Peroxisome Proliferator-Activated Receptor-gamma With Nuclear Factor kappa B and CCAAT/Enhancer- Binding Protein-beta
Tian, Qingping3; Miyazaki, Ryohei; Ichiki, Toshihiro1,2; Imayama, Ikuyo; Inanaga, Keita; Ohtsubo, Hideki; Yano, Kotaro; Takeda, Kotaro2; Sunagawa, Kenji
关键词Interleukin-6 Tnf-alpha Ppar Gamma Nf-kappa b C/ebp Beta
刊名HYPERTENSION
2009-05-01
DOI10.1161/HYPERTENSIONAHA.108.126656
53期:5页:798-804
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Peripheral Vascular Disease
研究领域[WOS]Cardiovascular System & Cardiology
关键词[WOS]SMOOTH-MUSCLE-CELLS ; CONVERTING-ENZYME-INHIBITORS ; C-REACTIVE PROTEIN ; ANGIOTENSIN-II ; PPAR-GAMMA ; HEART-FAILURE ; C/EBP-BETA ; BLOCKERS ; DISEASE ; GENE
英文摘要

Telmisartan, an angiotensin II type 1 receptor antagonist, was reported to be a partial agonist of peroxisome proliferator-activated receptor-gamma. Although peroxisome proliferator-activated receptor-gamma 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-alpha (TNF-alpha). Telmisartan decreased TNF-alpha-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-gamma antagonist, peroxisome proliferator-activated receptor-gamma may be involved in the process. Telmisartan suppressed IL-6 gene promoter activity induced by TNF-alpha. Deletion analysis suggested that the DNA segment between -150 bp and -27 bp of the IL-6 gene promoter that contains nuclear factor kappa B and CCAAT/enhancer-binding protein-beta sites was responsible for telmisartan suppression. Telmisartan attenuated TNF-alpha-induced nuclear factor kappa B- and CCAAT/enhancer-binding protein-beta-dependent gene transcription and DNA binding. Telmisartan also attenuated serum IL-6 level in TNF-alpha-infused mice and IL-6 production from rat aorta stimulated with TNF-alpha ex vivo. These data suggest that telmisartan may attenuate inflammatory process induced by TNF-alpha in addition to the blockade of angiotensin II type 1 receptor. Because both TNF-alpha 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. (Hypertension. 2009; 53: 798-804.)

语种英语
WOS记录号WOS:000265450400011
项目编号19590867
资助机构Ministry of Education, Culture, Sports, Science and Technology of Japan ; Japan-China Sasakawa Medical Fellowship
引用统计
被引频次:33[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/57169
专题北京大学第一临床医学院
北京大学第一临床医学院_老年病内科
作者单位1.Kyushu Univ, Grad Sch Med Sci, Dept Cardiovasc Med, Higashi Ku, Fukuoka 8128582, Japan
2.Kyushu Univ, Grad Sch Med Sci, Dept Adv Therapeut Cardiovasc Dis, Fukuoka 8128582, Japan
3.Peking Univ, Hosp 1, Fukuoka, Japan
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Tian, Qingping,Miyazaki, Ryohei,Ichiki, Toshihiro,et al. Inhibition of Tumor Necrosis Factor-alpha-Induced Interleukin-6 Expression by Telmisartan Through Cross-Talk of Peroxisome Proliferator-Activated Receptor-gamma With Nuclear Factor kappa B and CCAAT/Enhancer- Binding Protein-beta[J]. HYPERTENSION,2009,53(5):798-804.
APA Tian, Qingping.,Miyazaki, Ryohei.,Ichiki, Toshihiro.,Imayama, Ikuyo.,Inanaga, Keita.,...&Sunagawa, Kenji.(2009).Inhibition of Tumor Necrosis Factor-alpha-Induced Interleukin-6 Expression by Telmisartan Through Cross-Talk of Peroxisome Proliferator-Activated Receptor-gamma With Nuclear Factor kappa B and CCAAT/Enhancer- Binding Protein-beta.HYPERTENSION,53(5),798-804.
MLA Tian, Qingping,et al."Inhibition of Tumor Necrosis Factor-alpha-Induced Interleukin-6 Expression by Telmisartan Through Cross-Talk of Peroxisome Proliferator-Activated Receptor-gamma With Nuclear Factor kappa B and CCAAT/Enhancer- Binding Protein-beta".HYPERTENSION 53.5(2009):798-804.
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