TY - JOUR
T1 - Regulation of COX-2 expression and IL-6 release by particulate matter in airway epithelial cells
AU - Zhao, Yutong
AU - Usatyuk, Peter V.
AU - Gorshkova, Irina A.
AU - He, Donghong
AU - Wang, Ting
AU - Moreno-Vinasco, Liliana
AU - Geyh, Alison S.
AU - Breysse, Patrick N.
AU - Samet, Jonathan M.
AU - Spannhake, Ernst Wm
AU - Garcia, Joe G.N.
AU - Natarajan, Viswanathan
PY - 2009/1/1
Y1 - 2009/1/1
N2 - 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.
AB - 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.
KW - Airway epithelium
KW - Ambient particulate matter
KW - Cytokine
KW - Reactive oxygen species
KW - Transcriptional factors
UR - http://www.scopus.com/inward/record.url?scp=58149340589&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=58149340589&partnerID=8YFLogxK
U2 - 10.1165/rcmb.2008-0105OC
DO - 10.1165/rcmb.2008-0105OC
M3 - Article
C2 - 18617679
AN - SCOPUS:58149340589
SN - 1044-1549
VL - 40
SP - 19
EP - 30
JO - American journal of respiratory cell and molecular biology
JF - American journal of respiratory cell and molecular biology
IS - 1
ER -