title: Modulation of bronchial epithelial cells by IL-17.
abstract: BACKGROUND
  The induction of epithelial cytokines/chemokines is crucial in the migration of leukocytes, and its regulatory mechanisms remain incompletely defined.
  
  
  OBJECTIVE
  To determine the role of IL-17, a CD4(+) T cell-derived cytokine, in modulation of primary bronchial epithelial cells, the expression of IL-6, IL-8, and intercellular adhesion molecule 1 (ICAM-1) and the potential involvement of mitogen-activated protein (MAP) kinases in IL-17-mediated signaling were examined.
  
  
  METHODS
  The levels of gene expression and protein production for IL-6 and IL-8 in IL-17-treated cells, in the presence or absence of MAP kinase inhibitors, were analyzed by RT-PCR and ELISA, respectively, and activation of MAP kinases was determined by Western blot analyses.
  
  
  RESULTS
  We showed first that IL-17 induced time-dependent expression of IL-6 and IL-8 but not of the chemokines eotaxin and RANTES. In addition, IL-17 induced activation of extracellular signal-regulated kinase 1/2 but not of p38 or JNK kinases. A selective MAP kinase kinase inhibitor, PD98059, inhibited IL-17-induced IL-6 and IL-8. A combination of IL-17 and each of the cytokines IL-4, IL-13, and IFN-gamma further enhanced IL-8 expression. IL-17 alone did not induce ICAM-1 expression and showed no effect on IL-4- or IL-13-induced ICAM-1 expression. In contrast, a combination of IL-17 and IFN-gamma augmented IL-6 and ICAM-1 expression.
  
  
  CONCLUSIONS
  These findings suggest that IL-17, alone or in combination with other cytokines, modulates airway inflammation via-in part-the expression of epithelial IL-6, IL-8, and ICAM-1.
authors.affiliation: Asthma and Allergy Center, Johns Hopkins University, Baltimore, MD, USA.
authors.forename: M
authors.initials: M
authors.lastname: Kawaguchi
authors.forename: F
authors.initials: F
authors.lastname: Kokubu
authors.forename: H
authors.initials: H
authors.lastname: Kuga
authors.forename: S
authors.initials: S
authors.lastname: Matsukura
authors.forename: H
authors.initials: H
authors.lastname: Hoshino
authors.forename: K
authors.initials: K
authors.lastname: Ieki
authors.forename: T
authors.initials: T
authors.lastname: Imai
authors.forename: M
authors.initials: M
authors.lastname: Adachi
authors.forename: S K
authors.initials: SK
authors.lastname: Huang
mesh_terms: D001980:Bronchi / Q000166:cytology*; D002478:Cells, Cultured; D016207:Cytokines / Q000494:pharmacology; D004357:Drug Synergism; D004847:Epithelial Cells / Q000187:drug effects / Q000276:immunology; D005419:Flavonoids / Q000494:pharmacology; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis; D020381:Interleukin-17 / Q000494:pharmacology*; D015850:Interleukin-6 / Q000096:biosynthesis / Q000235:genetics; D016209:Interleukin-8 / Q000096:biosynthesis / Q000235:genetics; D007700:Kinetics; D020935:MAP Kinase Signaling System; D019950:Mitogen-Activated Protein Kinase 1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis; D020545:Respiratory Mucosa / Q000187:drug effects / Q000276:immunology*
chemical_list: D016207:Cytokines; D005419:Flavonoids; D020381:Interleukin-17; D015850:Interleukin-6; D016209:Interleukin-8; D012333:RNA, Messenger; D018799:Intercellular Adhesion Molecule-1; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one