Regulation of COX-2 expression and IL-6 release by particulate matter in airway epithelial cells

Yutong Zhao, Peter V. Usatyuk, Irina A. Gorshkova, Donghong He, Ting Wang, Liliana Moreno-Vinasco, Alison S. Geyh, Patrick N. Breysse, Jonathan M. Samet, Ernst Wm Spannhake, Joe G.N. Garcia, Viswanathan Natarajan

Research output: Contribution to journalArticle

61 Scopus citations

Abstract

Particulate matter (PM) in ambient air is a risk factor for human respiratory and cardiovascular diseases. The delivery of PM to airway epithelial cells has been linked to release of proinflammatory cytokines; however, the mechanisms of PM-induced inflammatory responses are not well-characterized. This study demonstrates that PM induces cyclooxygenase (COX)-2 expression and IL-6 release through both a reactive oxygen species (ROS)-dependent NF-κB pathway and an ROS-independent C/EBPβ pathway in human bronchial epithelial cells (HBEpCs) in culture. Treatment of HBEpCs with Baltimore PM induced ROS production, COX-2 expression, and IL-6 release. Pretreatment with N-acetylcysteine (NAC) or EUK-134, in a dose-dependent manner, attenuated PM-induced ROS production, COX-2 expression, and IL-6 release. The PM-induced ROS was significantly of mitochondrial origin, as evidenced by increased oxidation of the mitochondrially targeted hydroethidine to hydroxyethidium by reaction with superoxide. Exposure of HBEpCs to PM stimulated phosphorylation of NF-κB and C/EBPβ, while the NF-κB inhibitor, Bay11-7082, or C/EBPβ siRNA attenuated PM-induced COX-2 expression and IL-6 release. Furthermore, NAC or EUK-134 attenuated PM-induced activation of NF-κB; however, NAC or EUK-134 had no effect on phosphorylation of C/EBPβ. In addition, inhibition of COX-2 partly attenuated PM-induced Prostaglandin E2 and IL-6 release.

Original languageEnglish (US)
Pages (from-to)19-30
Number of pages12
JournalAmerican journal of respiratory cell and molecular biology
Volume40
Issue number1
DOIs
StatePublished - Jan 1 2009
Externally publishedYes

Keywords

  • Airway epithelium
  • Ambient particulate matter
  • Cytokine
  • Reactive oxygen species
  • Transcriptional factors

ASJC Scopus subject areas

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

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  • Cite this

    Zhao, Y., Usatyuk, P. V., Gorshkova, I. A., He, D., Wang, T., Moreno-Vinasco, L., Geyh, A. S., Breysse, P. N., Samet, J. M., Spannhake, E. W., Garcia, J. G. N., & Natarajan, V. (2009). Regulation of COX-2 expression and IL-6 release by particulate matter in airway epithelial cells. American journal of respiratory cell and molecular biology, 40(1), 19-30. https://doi.org/10.1165/rcmb.2008-0105OC