title: IL-27 enhances innate immunity of human pulmonary fibroblasts and epithelial cells through upregulation of TLR4 expression.
abstract: Lung tissue cells play an active role in the pathogenesis of pulmonary inflammatory diseases by releasing a variety of cytokines and chemokines. However, how lung tissue cells respond to microbial stimuli during pulmonary infections remains unclear. In this study, we found that patients with community-acquired pneumonia displayed increased IL-27 levels in bronchoalveolar lavage fluid and serum. We subsequently examined the immunopathological mechanisms for the activation of primary human lung fibroblasts and bronchial epithelial cells by IL-27. We demonstrated that IL-27 priming enhanced LPS-induced production of IL-6 and IL-8 from lung fibroblasts and bronchial epithelia cells via upregulating Toll-like receptor-4 (TLR4) expression. IL-27 upregulated TLR4 expression in lung fibroblasts through activation of Janus-activated kinase (JAK) and Jun NH2-terminal kinase (JNK) signaling pathways, and inhibition of the JAK pathway could partially decrease IL-27-induced TLR4 expression, while inhibition of JNK pathway could completely suppress IL-27-induced TLR4 expression. Our data suggest that IL-27 modulates innate immunity of lung tissue cells through upregulating TLR4 expression during pulmonary infections.
authors.affiliation: Department of Laboratory Medicine, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China; Key Laboratory of Diagnostic Medicine Designated by the Ministry of Education, Chongqing Medical University, Chongqing, China;
authors.forename: Yufeng
authors.initials: Y
authors.lastname: Su
authors.affiliation: Key Laboratory of Diagnostic Medicine Designated by the Ministry of Education, Chongqing Medical University, Chongqing, China;
authors.forename: Hua
authors.initials: H
authors.lastname: Yao
authors.affiliation: Key Laboratory of Diagnostic Medicine Designated by the Ministry of Education, Chongqing Medical University, Chongqing, China;
authors.forename: Hong
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Emergency and Intensive Care Unit, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China; and.
authors.forename: Fang
authors.initials: F
authors.lastname: Xu
authors.affiliation: Key Laboratory of Diagnostic Medicine Designated by the Ministry of Education, Chongqing Medical University, Chongqing, China;
authors.forename: Dagen
authors.initials: D
authors.lastname: Li
authors.affiliation: Department of Respiratory Diseases, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
authors.forename: Dairong
authors.initials: D
authors.lastname: Li
authors.affiliation: Key Laboratory of Diagnostic Medicine Designated by the Ministry of Education, Chongqing Medical University, Chongqing, China;
authors.forename: Xuemei
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Diagnostic Medicine Designated by the Ministry of Education, Chongqing Medical University, Chongqing, China;
authors.forename: Yibing
authors.initials: Y
authors.lastname: Yin
authors.affiliation: Department of Laboratory Medicine, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China; caoju723@163.com.
authors.forename: Ju
authors.initials: J
authors.lastname: Cao
mesh_terms: D004847:Epithelial Cells / Q000378:metabolism; D005347:Fibroblasts / Q000166:cytology* / Q000187:drug effects; D006801:Humans; D007113:Immunity, Innate / Q000187:drug effects* / Q000276:immunology; D064094:Interleukin-27 / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008168:Lung / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D051197:Toll-Like Receptor 4 / Q000276:immunology / Q000378:metabolism*; D015533:Transcriptional Activation; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D064094:Interleukin-27; D008070:Lipopolysaccharides; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4
keywords: IL-27; TLR4; epithelial cells; human lung fibroblasts; innate immunity