title: Exposure to PM2.5 induces aberrant activation of NF-κB in human airway epithelial cells by downregulating miR-331 expression.
abstract: Exposure to particulate matter (PM) with an aerodynamic diameter≤2.5μm (PM2.5) induces reactive oxygen species (ROS) and pro-inflammatory cytokine production, leading to airway epithelial injury. However, the mechanisms underlying the toxicity of PM2.5 have not been clarified. Here, we show that exposure to PM2.5 induces sustained activation of the nuclear factor kappa B (NF-κB) signaling in human airway epithelial Beas-2B (B2B) cells. In addition, PM2.5 exposure significantly decreased miR-331 expression in B2B cells, which was abrogated by inhibition of ROS or phosphoinositide 3-kinase (PI3K)/Akt pathway. Induction of miR-331 overexpression attenuated the PM2.5 exposure-induced NF-kBp65 nuclear translocation, IL-6 and IL-8 expression in B2B cells. Furthermore, miR-331 targeted the inhibitor of NF-κB kinase beta (IKK-β) by down-regulating the IKK-β-regulated luciferase activity in HEK293 cells. Moreover, induction of miR-331 over-expression inhibited IKK-β expression while induction of IKK-β over-expression prevented the inhibition of miR-331 on the PM2.5 exposure-induced NF-kBp65 nuclear translocation, IL-6 and IL-8 expression in B2B cells. Therefore, PM2.5 exposure decreased miR-331 expression via the ROS/PI3K/Akt pathway, resulting in an increase in the IKK-β expression and sustained NF-κB activation in human airway epithelial cells. Our findings may provide new insights into the molecular mechanisms underlying the toxicity of PM2.5 exposure and aid in design of new therapeutic strategies to prevent PM2.5-induced toxicity.
authors.affiliation: Department of Respiratory Medicine, the First Hospital of Jilin University, 71 Xinmin Street, Changchun, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Song
authors.affiliation: Department of Respiratory Medicine, the First Hospital of Jilin University, 71 Xinmin Street, Changchun, China.
authors.forename: Dan
authors.initials: D
authors.lastname: Li
authors.affiliation: Department of Pediatrics, the First Hospital of Jilin University, 71 Xinmin Street, Changchun, China.
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Li
authors.affiliation: Endoscopy Center, the China-Japan Hospital of Jilin University, 146 Xiantai Street, Changchun, China.
authors.forename: Lianjun
authors.initials: L
authors.lastname: Ma
authors.affiliation: Cadre's Ward, the First Hospital of Jilin University, 71 Xinmin Street, Changchun, China.
authors.forename: Xiaoxue
authors.initials: X
authors.lastname: Bai
authors.affiliation: Department of Respiratory Medicine, the First Hospital of Jilin University, 71 Xinmin Street, Changchun, China.
authors.forename: Zhongmei
authors.initials: Z
authors.lastname: Wen
authors.affiliation: Department of Respiratory Medicine, the First Hospital of Jilin University, 71 Xinmin Street, Changchun, China.
authors.forename: Xiufang
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Respiratory Medicine, the First Hospital of Jilin University, 71 Xinmin Street, Changchun, China.
authors.forename: Dong
authors.initials: D
authors.lastname: Chen
authors.affiliation: Department of Respiratory Medicine, the First Hospital of Jilin University, 71 Xinmin Street, Changchun, China,. Electronic address: plp640317@163.com.
authors.forename: Liping
authors.initials: L
authors.lastname: Peng
mesh_terms: D002460:Cell Line; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D057809:HEK293 Cells; D006801:Humans; D051550:I-kappa B Kinase / Q000235:genetics; D035683:MicroRNAs / Q000235:genetics*; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D052638:Particulate Matter / Q000633:toxicity*; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects
chemical_list: C544460:MIRN331 microRNA, human; D035683:MicroRNAs; D016328:NF-kappa B; D052638:Particulate Matter; D017382:Reactive Oxygen Species; D051550:I-kappa B Kinase; C496560:IKBKB protein, human
keywords: Inflammation; Lipopolysaccharide; NF-κB; PM2.5; Reactive oxygen species; microRNA