IL-17A promotes the growth of airway epithelial cells through ERK-dependent signaling pathway.
The effects of IL-17A on mucin production and growth of airway epithelial cells were examined. Histological and immunohistochemical analyses revealed that IL-17A increased the mucin production and number of tracheal epithelial cells in air-liquid interface cultures. The biological property of IL-17A to stimulate the mucin production by tracheal epithelial cells was determined using an ELISA. The mitogenic effect of IL-17A on tracheal epithelial cells was confirmed with Calcein-AM assay. The growth-stimulatory effect of IL-17A was dose-dependent and mediated via the ERK MAP kinase pathway. Inhibitors of MEK abrogated the mitogenic effect of IL-17A, whereas an inhibitor of p38 or JNK displayed no significant inhibitory effect. Moreover, relatively lower doses of IL-13 also significantly increased the growth of tracheal epithelial cells through a distinct signaling pathway from that of IL-17A. These findings provide the first evidence that IL-17A stimulates the growth of airway epithelial cells through the ERK MAP kinase pathway.
Inoue
Daisuke
D
Department of Geriatric and Respiratory Medicine, Tohoku University School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai 980-8574, Japan.
Numasaki
Muneo
M
Watanabe
Mika
M
Kubo
Hiroshi
H
Sasaki
Takahiko
T
Yasuda
Hiroyasu
H
Yamaya
Mutsuo
M
Sasaki
Hidetada
H
D000368:Aged; D002070:Butadienes / Q000494:pharmacology; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000502:physiology*; D005260:Female; D005419:Flavonoids / Q000494:pharmacology; D006801:Humans; D007150:Immunohistochemistry; D020381:Interleukin-17 / Q000494:pharmacology / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D055271:Mucin 5AC; D009077:Mucins / Q000096:biosynthesis; D009570:Nitriles / Q000494:pharmacology; D020545:Respiratory Mucosa / Q000166:cytology*; D015398:Signal Transduction / Q000502:physiology*; D014132:Trachea / Q000166:cytology* / Q000187:drug effects
D002070:Butadienes; D005419:Flavonoids; C508717:IL17A protein, human; D020381:Interleukin-17; C524678:MUC5AC protein, human; D055271:Mucin 5AC; D009077:Mucins; D009570:Nitriles; C113580:U 0126; D048049:Extracellular Signal-Regulated MAP Kinases; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one