Anti-inflammatory effects of thiazolidinediones in human airway smooth muscle cells

Ming Zhu, Lesley Flynt, Sanjukta Ghosh, Matt Mellema, Audreesh Banerjee, Erin Williams, Reynold A. Panettieri, Stephanie A. Shore

Research output: Contribution to journalArticle

29 Scopus citations

Abstract

Airway smooth muscle (ASM) cells have been reported to contribute to the inflammation of asthma. Because the thiazolidinediones (TZDs) exert anti-inflammatory effects, we examined the effects of troglitazone and rosiglitazone on the release of inflammatory moieties from cultured human ASM cells. Troglitazone dose-dependently reduced the IL-1β-induced release of IL-6 and vascular endothelial growth factor, the TNF-α-induced release of eotaxin and regulated on activation, normal T expressed and secreted (RANTES), and the IL-4-induced release of eotaxin. Rosiglitazone also inhibited the TNF-α-stimulated release of RANTES. Although TZDs are known to activate peroxisome proliferator-activated receptor-γ (PPARγ), these anti-inflammatory effects were not affected by a specific PPARγ inhibitor (GW 9662) or by the knockdown of PPARγ using short hairpin RNA. Troglitazone and rosiglitazone each caused the activation of adenosine monophosphate-activated protein kinase (AMPK), as detected by Western blotting using a phospho-AMPK antibody. The anti-inflammatory effects of TZDs were largely mimicked by the AMPK activators, 5-amino-4-imidazolecarboxamide ribose (AICAR) and metformin. However, the AMPK inhibitors, Ara A and Compound C, were not effective in preventing the antiinflammatory effects of troglitazone or rosiglitzone, suggesting that the effects of these TZDs are likely not mediated through the activation of AMPK. These data indicate that TZDs inhibit the release of a variety of inflammatory mediators from human ASM cells, suggesting that they may be useful in the treatment of asthma, and the data also indicate that the effects of TZDs are not mediated by PPARγ or AMPK.

Original languageEnglish (US)
Pages (from-to)111-119
Number of pages9
JournalAmerican Journal of Respiratory Cell and Molecular Biology
Volume45
Issue number1
DOIs
StatePublished - Jul 1 2011
Externally publishedYes

Keywords

  • Anti-inflammatory
  • IL-1β
  • PPARγ
  • shRNA
  • TNF-α

ASJC Scopus subject areas

  • Cell Biology
  • Pulmonary and Respiratory Medicine
  • Molecular Biology
  • Clinical Biochemistry

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  • Cite this

    Zhu, M., Flynt, L., Ghosh, S., Mellema, M., Banerjee, A., Williams, E., Panettieri, R. A., & Shore, S. A. (2011). Anti-inflammatory effects of thiazolidinediones in human airway smooth muscle cells. American Journal of Respiratory Cell and Molecular Biology, 45(1), 111-119. https://doi.org/10.1165/rcmb.2009-0445OC