Wood Smoke Enhances Cigarette Smoke-Induced Inflammation by Inducing the Aryl Hydrocarbon Receptor Repressor in Airway Epithelial Cells

被引:34
作者
Awji, Elias G. [1 ]
Chand, Hitendra [1 ]
Bruse, Shannon [1 ]
Smith, Kevin R. [1 ]
Colby, Jennifer K. [2 ]
Mebratu, Yohannes [1 ]
Levy, Bruce D. [2 ]
Tesfaigzi, Yohannes [1 ]
机构
[1] Lovelace Resp Res Inst, COPD Program, Albuquerque, NM 87108 USA
[2] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Pulm & Crit Care Med, Boston, MA 02115 USA
基金
美国国家卫生研究院;
关键词
arachidonic acid pathway; air pollution; neutrophilic inflammation; exacerbation; lipoxin; OBSTRUCTIVE PULMONARY-DISEASE; SUBCHRONIC EXPOSURE; LUNG INFLAMMATION; DIOXIN RECEPTOR; LIPOXIN A(4); AMBIENT AIR; CYCLOOXYGENASE-2; RESOLUTION; RATS; EXPRESSION;
D O I
10.1165/rcmb.2014-0142OC
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Our previous studies showed that cigarette smokers who are exposed to wood smoke (WS) are at an increased risk for chronic bronchitis and reduced lung function. The present study was undertaken to determine the mechanisms for WS-induced adverse effects. We studied the effect of WS exposure using four cohorts of mice. C57Bl/6 mice were exposed for 4 or 12 weeks to filtered air, to 10 mg/m(3) WS for 2 h/d, to 250 mg/m(3) cigarette smoke (CS) for 6 h/d, or to CS followed by WS(CW). Inflammation was absent in the filtered air and WS groups, but enhanced by twofold in the bronchoalveolar lavage of the CW compared with CS group as measured by neutrophil numbers and levels of the neutrophil chemoattractant, keratinocyte-derived chemokine. The levels of the anti-inflammatory lipoxin, lipoxin A4, were reduced by threefold along with cyclo-oxygenase (COX)-2 and microsomal prostaglandin E synthase (mPGES)-1 in airway epithelial cells and PGE(2) levels in the bronchoalveolar lavage of CW compared with CS mice. We replicated, in primary human airway epithelial cells, the changes observed in mice. Immunoprecipitations showed that WS blocked the interaction of aryl hydrocarbon receptor (AHR) with AHR nuclear transporter to reduce expression of COX-2 and mPGES-1 by increasing expression of AHR repressor (AHRR). Collectively, these studies show that exposure to low concentrations of WS enhanced CS-induced inflammation by inducing AHRR expression to suppress AHR, COX-2, and mPGES-1 expression, and levels of PGE2 and lipoxin A4. Therefore, AHRR is a potential therapeutic target for WS-associated exacerbations of CS-induced inflammation.
引用
收藏
页码:377 / 386
页数:10
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