TY - JOUR
T1 - Modulation of bronchial epithelial cells by IL-17
AU - Kawaguchi, Mio
AU - Kokubu, Fumio
AU - Kuga, Hideki
AU - Matsukura, Satoshi
AU - Hoshino, Hiroshi
AU - Ieki, Koushi
AU - Imai, Toshimichi
AU - Adachi, Mitsuru
AU - Huang, Shau Ku
PY - 2001
Y1 - 2001
N2 - 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.
AB - 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.
KW - Adhesion molecule
KW - Bronchial epithelial cell
KW - ERKl/2
KW - Interleukin-17
KW - Interleukin-6
KW - Interleukin-8
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UR - http://www.scopus.com/inward/citedby.url?scp=0035179395&partnerID=8YFLogxK
U2 - 10.1067/mai.2001.119027
DO - 10.1067/mai.2001.119027
M3 - Article
C2 - 11692108
AN - SCOPUS:0035179395
SN - 0091-6749
VL - 108
SP - 804
EP - 809
JO - Journal of Allergy and Clinical Immunology
JF - Journal of Allergy and Clinical Immunology
IS - 5
ER -