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

28 Citations (Scopus)

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

Fingerprint

troglitazone
Thiazolidinediones
rosiglitazone
Adenosine Monophosphate
Smooth Muscle Myocytes
Peroxisome Proliferator-Activated Receptors
Anti-Inflammatory Agents
Protein Kinases
Asthma
Vidarabine
Ribose
Metformin
Protein Kinase Inhibitors
Interleukin-1
Interleukin-4
Vascular Endothelial Growth Factor A
Small Interfering RNA
Interleukin-6
Western Blotting
Inflammation

All Science Journal Classification (ASJC) codes

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

Keywords

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

Cite this

Zhu, Ming ; Flynt, Lesley ; Ghosh, Sanjukta ; Mellema, Matt ; Banerjee, Audreesh ; Williams, Erin ; Panettieri, Reynold A. ; Shore, Stephanie A. / Anti-inflammatory effects of thiazolidinediones in human airway smooth muscle cells. In: American journal of respiratory cell and molecular biology. 2011 ; Vol. 45, No. 1. pp. 111-119.
@article{154299af4b9d477881775c7d20392451,
title = "Anti-inflammatory effects of thiazolidinediones in human airway smooth muscle cells",
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.",
keywords = "Anti-inflammatory, IL-1β, PPARγ, TNF-α, shRNA",
author = "Ming Zhu and Lesley Flynt and Sanjukta Ghosh and Matt Mellema and Audreesh Banerjee and Erin Williams and Panettieri, {Reynold A.} and Shore, {Stephanie A.}",
year = "2011",
month = "7",
day = "1",
doi = "https://doi.org/10.1165/rcmb.2009-0445OC",
language = "English (US)",
volume = "45",
pages = "111--119",
journal = "American Journal of Respiratory Cell and Molecular Biology",
issn = "1044-1549",
publisher = "American Thoracic Society",
number = "1",

}

Anti-inflammatory effects of thiazolidinediones in human airway smooth muscle cells. / Zhu, Ming; Flynt, Lesley; Ghosh, Sanjukta; Mellema, Matt; Banerjee, Audreesh; Williams, Erin; Panettieri, Reynold A.; Shore, Stephanie A.

In: American journal of respiratory cell and molecular biology, Vol. 45, No. 1, 01.07.2011, p. 111-119.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Anti-inflammatory effects of thiazolidinediones in human airway smooth muscle cells

AU - Zhu, Ming

AU - Flynt, Lesley

AU - Ghosh, Sanjukta

AU - Mellema, Matt

AU - Banerjee, Audreesh

AU - Williams, Erin

AU - Panettieri, Reynold A.

AU - Shore, Stephanie A.

PY - 2011/7/1

Y1 - 2011/7/1

N2 - 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.

AB - 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.

KW - Anti-inflammatory

KW - IL-1β

KW - PPARγ

KW - TNF-α

KW - shRNA

UR - http://www.scopus.com/inward/record.url?scp=80051557836&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=80051557836&partnerID=8YFLogxK

U2 - https://doi.org/10.1165/rcmb.2009-0445OC

DO - https://doi.org/10.1165/rcmb.2009-0445OC

M3 - Article

C2 - 20870897

VL - 45

SP - 111

EP - 119

JO - American Journal of Respiratory Cell and Molecular Biology

JF - American Journal of Respiratory Cell and Molecular Biology

SN - 1044-1549

IS - 1

ER -