title: Eicosapentaenoic acid attenuates cigarette smoke-induced lung inflammation by inhibiting ROS-sensitive inflammatory signaling.
abstract: Cigarette smoking causes chronic lung inflammation that is mainly regulated by redox-sensitive pathways. Our previous studies have demonstrated that cigarette smoke (CS) activates reactive oxygen species (ROS)-sensitive mitogen-activated protein kinases (MAPKs)/nuclear factor-κB (NF-κB) signaling resulting in induction of lung inflammation. Eicosapentaenoic acid (EPA), a major type of omega-3 polyunsaturated fatty acid, is present in significant amounts in marine-based fish and fish oil. EPA has been shown to possess antioxidant and anti-inflammatory properties in vitro and in vivo. However, whether EPA has similar beneficial effects against CS-induced lung inflammation remains unclear. Using a murine model, we show that subchronic CS exposure for 4 weeks caused pulmonary inflammatory infiltration (total cell count in bronchoalveolar lavage fluid (BALF), 11.0-fold increase), increased lung vascular permeability (protein level in BALF, 3.1-fold increase), elevated levels of chemokines (11.4-38.2-fold increase) and malondialdehyde (an oxidative stress biomarker; 2.0-fold increase) in the lungs, as well as lung inflammation; all of these CS-induced events were suppressed by daily supplementation with EPA. Using human bronchial epithelial cells, we further show that CS extract (CSE) sequentially activated NADPH oxidase (NADPH oxidase activity, 1.9-fold increase), increased intracellular levels of ROS (3.0-fold increase), activated both MAPKs and NF-κB, and induced interleukin-8 (IL-8; 8.2-fold increase); all these CSE-induced events were inhibited by pretreatment with EPA. Our findings suggest a novel role for EPA in alleviating the oxidative stress and lung inflammation induced by subchronic CS exposure in vivo and in suppressing the CSE-induced IL-8 in vitro via its antioxidant function and by inhibiting MAPKs/NF-κB signaling.
authors.affiliation: Department of Physiology, School of Medicine, National Yang-Ming University Taipei, Taiwan.
authors.forename: Meng-Han
authors.initials: MH
authors.lastname: Liu
authors.affiliation: Department of Physiology, School of Medicine, National Yang-Ming University Taipei, Taiwan.
authors.forename: An-Hsuan
authors.initials: AH
authors.lastname: Lin
authors.affiliation: Department of Urology, Taipei City Hospital, Zhong-Xiao Branch Taipei, Taiwan.
authors.forename: Shing-Hwa
authors.initials: SH
authors.lastname: Lu
authors.affiliation: Hsin Sheng Junior College of Medical Care and Management Longtan Township, Taiwan.
authors.forename: Ruo-Yun
authors.initials: RY
authors.lastname: Peng
authors.affiliation: Department of Physiology, School of Medicine, National Yang-Ming University Taipei, Taiwan.
authors.forename: Tzong-Shyuan
authors.initials: TS
authors.lastname: Lee
authors.affiliation: Department of Physiology, School of Medicine, National Yang-Ming University Taipei, Taiwan.
authors.forename: Yu Ru
authors.initials: YR
authors.lastname: Kou
keywords: chemokines; cigarette smoke; eicosapentaenoic acid; lung epithelial cells; lung inflammation; reactive oxygen species; signal transduction