title: Regulation of COX-2 expression and IL-6 release by particulate matter in airway epithelial cells.
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-kappaB pathway and an ROS-independent C/EBPbeta 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-kappaB and C/EBPbeta, while the NF-kappaB inhibitor, Bay11-7082, or C/EBPbeta siRNA attenuated PM-induced COX-2 expression and IL-6 release. Furthermore, NAC or EUK-134 attenuated PM-induced activation of NF-kappaB; however, NAC or EUK-134 had no effect on phosphorylation of C/EBPbeta. In addition, inhibition of COX-2 partly attenuated PM-induced Prostaglandin E2 and IL-6 release.
authors.affiliation: Department of Medicine, University of Chicago, Chicago, IL 60637, USA.
authors.forename: Yutong
authors.initials: Y
authors.lastname: Zhao
authors.forename: Peter V
authors.initials: PV
authors.lastname: Usatyuk
authors.forename: Irina A
authors.initials: IA
authors.lastname: Gorshkova
authors.forename: Donghong
authors.initials: D
authors.lastname: He
authors.forename: Ting
authors.initials: T
authors.lastname: Wang
authors.forename: Liliana
authors.initials: L
authors.lastname: Moreno-Vinasco
authors.forename: Alison S
authors.initials: AS
authors.lastname: Geyh
authors.forename: Patrick N
authors.initials: PN
authors.lastname: Breysse
authors.forename: Jonathan M
authors.initials: JM
authors.lastname: Samet
authors.forename: Ernst Wm
authors.initials: EW
authors.lastname: Spannhake
authors.forename: Joe G N
authors.initials: JG
authors.lastname: Garcia
authors.forename: Viswanathan
authors.initials: V
authors.lastname: Natarajan
mesh_terms: D000111:Acetylcysteine / Q000378:metabolism; D015142:Baltimore; D022782:CCAAT-Enhancer-Binding Protein-beta / Q000235:genetics / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism*; D016207:Cytokines / Q000378:metabolism; D015232:Dinoprostone / Q000235:genetics / Q000378:metabolism; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism*; D008928:Mitochondria / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D009942:Organometallic Compounds / Q000378:metabolism; D052638:Particulate Matter / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D020545:Respiratory Mucosa / Q000166:cytology* / Q000378:metabolism; D012459:Salicylates / Q000378:metabolism
chemical_list: D022782:CCAAT-Enhancer-Binding Protein-beta; D016207:Cytokines; C433928:EUK-134; D015850:Interleukin-6; D016328:NF-kappa B; D009942:Organometallic Compounds; D052638:Particulate Matter; D034741:RNA, Small Interfering; D017382:Reactive Oxygen Species; D012459:Salicylates; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D015232:Dinoprostone; D000111:Acetylcysteine