IL-17F Induces CCL20 in Bronchial Epithelial Cells.
IL-17F plays a crucial role in airway inflammatory diseases including asthma, but its function has not been fully elucidated. CCL20 is also involved in allergic airway inflammation, while its regulatory mechanisms remain to be defined. To further identify a novel role of IL-17F, the expression of CCL20 by IL-17F in bronchial epithelial cells and the signaling mechanisms involved were investigated. Bronchial epithelial cells were stimulated with IL-17F, and the levels of CCL20 gene and protein measured, with the effects of the addition of various kinase inhibitors and siRNAs also investigated. IL-17F significantly induced the expression of CCL20 gene and protein. Pretreatment with inhibitors for MEK1/2, Raf1 and MSK1, and overexpression of a Raf1 dominant-negative mutant significantly diminished IL-17F-induced CCL20 production. Moreover, transfection of the siRNAs targeting MSK1, p90RSK, and CREB blocked CCL20 expression. These findings suggest that IL-17F is able to induce CCL20 via Raf1-MEK1/2-ERK1/2-MSK1/p90RSK-CREB signaling pathway in bronchial epithelial cells. The IL-17F/CCL20 axis may be a novel pharmacological target for asthma.
Department of Respiratory Medicine, Institute of Clinical Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 3058575, Japan.
Kyoko
K
Nozato
Junichi
J
Fujita
Mio
M
Kawaguchi
Gen
G
Ohara
Yuko
Y
Morishima
Yukio
Y
Ishii
Shau-Ku
SK
Huang
Fumio
F
Kokubu
Hiroaki
H
Satoh
Nobuyuki
N
Hizawa