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Published ahead of print on July 10, 2008
Am. J. Respir. Cell Mol. Biol. 2008, doi:10.1165/rcmb.2008-0105OC
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Submitted on March 17, 2008
Revised on July 10, 2008

Regulation of COX-2 Expression and IL-6 Release by Particulate Matter in Airway Epithelial Cells

Yutong Zhao1, Peter V Usatyuk1, Irina A Gorshkova1, Donghong He1, Ting Wang1, Liliana Moreno-Vinasco1, Alison S Geyh2, Patrick N Breysse2, Jonathan M Samet3, Ernst Wm Spannhake2, Joe G.N. Garcia1, and Viswanathan Natarajan1*

1 Department of Medicine, The University of Chicago, Chicago, IL, USA, 2 Department of Environmental Health Sciences, Johns Hopkins University, Bloomberg School of Public Health, Baltimore, MD, USA, 3 Department of Epidemiology, Johns Hopkins University, Bloomberg School of Public Health, Baltimore, MD, USA

* To whom correspondence should be addressed. E-mail: vnataraj{at}medicine.bsd.uchicago.edu.

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 pro-inflammatory cytokines; however, the mechanisms of PM-induced inflammatory responses are not well-characterized. This study demonstrates that PM induces cyclooxygenase (COX)-2 expression and interleukin (IL)-6 release through both a reactive oxygen species (ROS)-dependent NF-{kappa}B pathway and a ROS-independent C/EBP{beta} 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-{kappa}B and C/EBP{beta}, while the NF-{kappa}B inhibitor, Bay11-7082, or C/EBP{beta} siRNA attenuated PM-induced COX-2 expression and IL-6 release. Furthermore, NAC or EUK-134 attenuated PM-induced activation of NF-{kappa}B; however, NAC or EUK-134 had no effect on phosphorylation of C/EBP{beta}. Additionally, inhibition of COX-2 partly attenuated PM-induced PGE2 and IL-6 release.






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