Telmisartan inhibits cytokine-induced nuclear factor-kappaB activation independently of the peroxisome proliferator-activated receptor-gamma

Hypertens Res. 2009 Sep;32(9):765-9. doi: 10.1038/hr.2009.95. Epub 2009 Jul 10.


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.

MeSH terms

  • Angiotensin II Type 1 Receptor Blockers / pharmacology*
  • Anilides / pharmacology
  • Benzimidazoles / pharmacology*
  • Benzoates / pharmacology*
  • Biotransformation / drug effects
  • Blotting, Western
  • Cells, Cultured
  • Cyclic AMP-Dependent Protein Kinases / metabolism
  • Cytokines / antagonists & inhibitors*
  • Cytokines / biosynthesis
  • Cytokines / physiology
  • Dose-Response Relationship, Drug
  • Gene Expression / drug effects
  • Humans
  • Hypoglycemic Agents / pharmacology
  • Metformin / pharmacology
  • NF-kappa B / antagonists & inhibitors
  • NF-kappa B / metabolism*
  • PPAR gamma / biosynthesis
  • PPAR gamma / drug effects
  • PPAR gamma / metabolism*
  • RNA, Messenger / biosynthesis
  • RNA, Messenger / genetics
  • Reverse Transcriptase Polymerase Chain Reaction
  • Telmisartan
  • Tumor Necrosis Factor-alpha / biosynthesis
  • Tumor Necrosis Factor-alpha / genetics
  • Vascular Cell Adhesion Molecule-1 / biosynthesis
  • Vascular Cell Adhesion Molecule-1 / genetics


  • 2-chloro-5-nitrobenzanilide
  • Angiotensin II Type 1 Receptor Blockers
  • Anilides
  • Benzimidazoles
  • Benzoates
  • Cytokines
  • Hypoglycemic Agents
  • NF-kappa B
  • PPAR gamma
  • RNA, Messenger
  • Tumor Necrosis Factor-alpha
  • Vascular Cell Adhesion Molecule-1
  • Metformin
  • Cyclic AMP-Dependent Protein Kinases
  • Telmisartan