Interleukin-17A and Toll-Like Receptor 3 Ligand Poly(I:C) Synergistically Induced Neutrophil Chemoattractant Production by Bronchial Epithelial Cells.
Chronic inflammatory airway diseases, such as bronchial asthma and chronic obstructive pulmonary disease, are common respiratory disorders worldwide. Exacerbations of these diseases are frequent and worsen patients' respiratory condition and overall health. However, the mechanisms of exacerbation have not been fully elucidated. Recently, it was reported that interleukin (IL)-17A might play an important role in neutrophilic inflammation, which is characteristic of such exacerbations, through increased production of neutrophil chemoattractants. Therefore, we hypothesized that IL-17A was involved in the pathogenesis of acute exacerbation, due to viral infection in chronic inflammatory airway diseases. In this study, we assessed chemokine production by bronchial epithelial cells and investigated the underlying mechanisms. Comprehensive chemokine analysis showed that, compared with poly(I:C) alone, co-stimulation of BEAS-2B cells with IL-17A and poly(I:C) strongly induced production of such neutrophil chemoattractants as CXC chemokine ligand (CXCL)8, growth-related oncogene (GRO), and CXCL1. Co-stimulation synergistically induced CXCL8 and CXCL1 mRNA and protein production by BEAS-2B cells and normal human bronchial epithelial cells. Poly(I:C) induced chemokine expression by BEAS-2B cells mainly via Toll-like receptor 3/TIR-domain-containing adapter-inducing interferon-β-mediated signals. The co-stimulation with IL-17A and poly(I:C) markedly activated the p38 and extracellular-signal-regulated kinase 1/2 pathway, compared with poly(I:C), although there was little change in nuclear factor-κB translocation into the nucleus or the transcriptional activities of nuclear factor-κB and activator protein 1. IL-17A promoted stabilization of CXCL8 mRNA in BEAS-2B cells treated with poly(I:C). In conclusion, IL-17A appears to be involved in the pathogenesis of chronic inflammatory airway disease exacerbation, due to viral infection by promoting release of neutrophil chemoattractants from bronchial epithelial cells.
Department of Respiratory Medicine, Graduate School of Medicine, the University of Tokyo, Tokyo, Japan.
Hirotaka
H
Matsuzaki
Department of Respiratory Medicine, Graduate School of Medicine, the University of Tokyo, Tokyo, Japan; Department of Clinical Laboratory, the University of Tokyo Hospital, Tokyo, Japan.
Yu
Y
Mikami
Department of Respiratory Medicine, Graduate School of Medicine, the University of Tokyo, Tokyo, Japan.
Kousuke
K
Makita
Department of Respiratory Medicine, Graduate School of Medicine, the University of Tokyo, Tokyo, Japan.
Hideyuki
H
Takeshima
Department of Respiratory Medicine, Graduate School of Medicine, the University of Tokyo, Tokyo, Japan; Division of Health Service Promotion, the University of Tokyo, Tokyo, Japan.
Masafumi
M
Horie
Department of Respiratory Medicine, Graduate School of Medicine, the University of Tokyo, Tokyo, Japan.
Satoshi
S
Noguchi
Department of Respiratory Medicine, Graduate School of Medicine, the University of Tokyo, Tokyo, Japan; Division of Health Service Promotion, the University of Tokyo, Tokyo, Japan.
Taisuke
T
Jo
Department of Respiratory Medicine, Graduate School of Medicine, the University of Tokyo, Tokyo, Japan.
Osamu
O
Narumoto
Fourth Department of Internal Medicine, Teikyo University School of Medicine, Mizonokuchi Hospital, Kanagawa, Japan.
Tadashi
T
Kohyama
Department of Respiratory Medicine, Kyorin University School of Medicine, Tokyo, Japan.
Hajime
H
Takizawa
Department of Respiratory Medicine, Graduate School of Medicine, the University of Tokyo, Tokyo, Japan.
Takahide
T
Nagase
Department of Respiratory Medicine, Graduate School of Medicine, the University of Tokyo, Tokyo, Japan.
Yasuhiro
Y
Yamauchi
D001249:Asthma / Q000235:genetics* / Q000473:pathology; D001980:Bronchi / Q000378:metabolism* / Q000473:pathology; D054360:Chemokine CXCL1 / Q000235:genetics / Q000378:metabolism; D002630:Chemotactic Factors / Q000096:biosynthesis / Q000378:metabolism*; D004847:Epithelial Cells / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D020381:Interleukin-17 / Q000096:biosynthesis / Q000378:metabolism*; D016209:Interleukin-8 / Q000235:genetics / Q000378:metabolism; D008024:Ligands; D009504:Neutrophils / Q000378:metabolism; D011070:Poly I-C / Q000235:genetics* / Q000378:metabolism; D051196:Toll-Like Receptor 3 / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000235:genetics
C508606:CXCL8 protein, human; D054360:Chemokine CXCL1; D002630:Chemotactic Factors; C508717:IL17A protein, human; D020381:Interleukin-17; D016209:Interleukin-8; D008024:Ligands; D051196:Toll-Like Receptor 3; D048051:p38 Mitogen-Activated Protein Kinases; D011070:Poly I-C