title: YKL-40 induces IL-8 expression from bronchial epithelium via MAPK (JNK and ERK) and NF-κB pathways, causing bronchial smooth muscle proliferation and migration.
abstract: Recently, the serum levels of YKL-40, a chitinase-like glycoprotein, have been shown to be significantly elevated in asthmatics and are associated with asthma severity. Although these studies raise the possibility that YKL-40 may influence asthma, the mechanisms remain unknown. This study firstly investigated the mechanisms involved in YKL-40-mediated inflammation in human bronchial epithelial cells (HBECs) and analyzed the soluble factors secreted by bronchial epithelial cells exposed to YKL-40 that were responsible for increasing proliferation and migration of primary normal human bronchial smooth muscle cells (BSMCs). YKL-40-induced inflammation was assayed in two HBECs (BEAS-2B cell line and primary HBECs). In addition, we treated BEAS-2B cells and HBECs with YKL-40 and added the conditioned culture media to BSMCs. The proliferation and migration of BSMCs were determined by premixed WST-1 cell proliferation reagent (Clontech Laboratories) and QCM chemotaxis migration assay (Millipore), respectively. Bronchial epithelial cells treated with YKL-40 resulted in a significant increase of IL-8 production, which was dependent on MAPK (JNK and ERK) and NF-κB pathways activation. YKL-40-induced IL-8 was found to further stimulate proliferation and migration of BSMCs, and the effects were inhibited after neutralizing IL-8. Through investigating the interaction of airway epithelium and smooth muscle, our findings implicate that YKL-40 may be involved in the inflammation of asthma by induction of IL-8 from epithelium, subsequently contributing to BSMC proliferation and migration. Moreover, inhibition of IL-8 signaling is a potential therapeutic target for YKL-40-induced inflammation and remodeling of asthma.
authors.affiliation: Department of Respiratory Medicine, Changzheng Hospital, Second Military Medical University, Shanghai 200003, People's Republic of China.
authors.forename: Hao
authors.initials: H
authors.lastname: Tang
authors.forename: Yu
authors.initials: Y
authors.lastname: Sun
authors.forename: Zhaoquan
authors.initials: Z
authors.lastname: Shi
authors.forename: Hai
authors.initials: H
authors.lastname: Huang
authors.forename: Zheng
authors.initials: Z
authors.lastname: Fang
authors.forename: Jiquan
authors.initials: J
authors.lastname: Chen
authors.forename: Qingyu
authors.initials: Q
authors.lastname: Xiu
authors.forename: Bing
authors.initials: B
authors.lastname: Li
mesh_terms: D054392:Adipokines / Q000502:physiology*; D001249:Asthma / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D001980:Bronchi / Q000201:enzymology / Q000276:immunology* / Q000473:pathology; D002461:Cell Line, Transformed; D002465:Cell Movement / Q000276:immunology*; D049109:Cell Proliferation; D000071451:Chitinase-3-Like Protein 1; D048049:Extracellular Signal-Regulated MAP Kinases / Q000502:physiology; D006801:Humans; D018836:Inflammation Mediators / Q000502:physiology; D016209:Interleukin-8 / Q000096:biosynthesis*; D048031:JNK Mitogen-Activated Protein Kinases / Q000502:physiology; D037102:Lectins / Q000502:physiology*; D020935:MAP Kinase Signaling System / Q000276:immunology*; D009130:Muscle, Smooth / Q000201:enzymology / Q000276:immunology / Q000473:pathology; D016328:NF-kappa B / Q000502:physiology*; D020545:Respiratory Mucosa / Q000201:enzymology / Q000276:immunology* / Q000473:pathology; D015398:Signal Transduction / Q000276:immunology; D015854:Up-Regulation / Q000276:immunology
chemical_list: D054392:Adipokines; C084533:CHI3L1 protein, human; C508606:CXCL8 protein, human; D000071451:Chitinase-3-Like Protein 1; D018836:Inflammation Mediators; D016209:Interleukin-8; D037102:Lectins; D016328:NF-kappa B; D048049:Extracellular Signal-Regulated MAP Kinases; D048031:JNK Mitogen-Activated Protein Kinases