Modulation of bronchial epithelial cells by IL-17

Mio Kawaguchi, Fumio Kokubu, Hideki Kuga, Satoshi Matsukura, Hiroshi Hoshino, Koushi Ieki, Toshimichi Imai, Mitsuru Adachi, Shau Ku Huang

Research output: Contribution to journalArticlepeer-review

139 Citations (Scopus)

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-γ 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-γ augmented IL-6 and ICAM-1 expression. Conclusion: 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.

Original languageEnglish
Pages (from-to)804-809
Number of pages6
JournalJournal of Allergy and Clinical Immunology
Volume108
Issue number5
DOIs
Publication statusPublished - 2001

Keywords

  • Adhesion molecule
  • Bronchial epithelial cell
  • ERKl/2
  • Interleukin-17
  • Interleukin-6
  • Interleukin-8

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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