Telmisartan inhibits cytokine-induced nuclear factor-kappaB activation independently of the peroxisome proliferator-activated receptor-gamma.
Telmisartan is an angiotensin-II type 1 receptor (AT1R) blocker, currently used to treat patients with hypertension. Telmisartan, in addition to its effect on AT1R, is thought to activate the nuclear transcription factor, peroxisome proliferator-activated receptor-gamma (PPAR gamma), thereby acting as a partial PPAR gamma agonist. This study was conducted to examine whether telmisartan might suppress cytokine-induced inflammatory signaling in vascular endothelial cells, thereby attenuating cellular inflammation possibly by PPAR gamma activation. Telmisartan caused a dose-dependent suppression of the tumor necrosis factor-alpha (TNFalpha)-induced activation of nuclear factor (NF)-kappaB in vascular endothelial cells in this study. The PPAR gamma antagonist, GW9662, did not influence the inhibitory effect of telmisartan on NF-kappaB activation. The thiazolidinediones neither influenced TNFalpha-induced NF-kappaB activation nor influenced the inhibitory effect of telmisartan in this process. Telmisartan dose dependently diminished the TNFalpha-induced gene expression of VCAM-1, and GW9662 did not attenuate this effect. Thus, telmisartan inhibits the cytokine-induced expression of the VCAM-1 gene by blocking NF-kappaB activation independently of PPAR gamma activation. Although the mechanism by which this occurs remains unclear, our findings suggest that telmisartan-induced anti-inflammatory effects might have favorable effects on vasculature in hypertensive patients.
Nakano
Ayuko
A
Department of Endocrinology and Metabolism, Dokkyo University School of Medicine, Mibu, Tochigi, Japan.
Hattori
Yoshiyuki
Y
Aoki
Chie
C
Jojima
Teruo
T
Kasai
Kikuo
K
D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology*; D000813:Anilides / Q000494:pharmacology; D001562:Benzimidazoles / Q000494:pharmacology*; D001565:Benzoates / Q000494:pharmacology*; D001711:Biotransformation / Q000187:drug effects; D015153:Blotting, Western; D002478:Cells, Cultured; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D016207:Cytokines / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology; D008687:Metformin / Q000494:pharmacology; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism*; D047495:PPAR gamma / Q000096:biosynthesis / Q000187:drug effects / Q000378:metabolism*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000077333:Telmisartan; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000235:genetics; D019010:Vascular Cell Adhesion Molecule-1 / Q000096:biosynthesis / Q000235:genetics
C457499:2-chloro-5-nitrobenzanilide; D047228:Angiotensin II Type 1 Receptor Blockers; D000813:Anilides; D001562:Benzimidazoles; D001565:Benzoates; D016207:Cytokines; D007004:Hypoglycemic Agents; D016328:NF-kappa B; D047495:PPAR gamma; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1; D008687:Metformin; D017868:Cyclic AMP-Dependent Protein Kinases; D000077333:Telmisartan