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Induction of insulin‐like growth factor‐I by interleukin‐17F in bronchial epithelial cells
Author(s) -
Kawaguchi M.,
Fujita J.,
Kokubu F.,
Ohara G.,
Huang S.K.,
Matsukura S.,
Ishii Y.,
Adachi M.,
Satoh H.,
Hizawa N.
Publication year - 2010
Publication title -
clinical and experimental allergy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.462
H-Index - 154
eISSN - 1365-2222
pISSN - 0954-7894
DOI - 10.1111/j.1365-2222.2010.03527.x
Subject(s) - ribosomal s6 kinase , small interfering rna , creb , kinase , microbiology and biotechnology , protein kinase a , mitogen activated protein kinase , transfection , insulin like growth factor , biology , cancer research , mapk/erk pathway , growth factor , signal transduction , cell culture , transcription factor , p70 s6 kinase 1 , protein kinase b , biochemistry , receptor , gene , genetics
Summary Cite this as: M. Kawaguchi, J. Fujita, F. Kokubu, G. Ohara, S‐K Huang, S. Matsukura, Y. Ishii, M. Adachi, H. Satoh and N. Hizawa, Clinical & Experimental Allergy, 2010 (40) 1036–1043. Background Increased expression of IL‐17F has been noted in the airway of asthmatic patients, but its role in asthma has not been fully elucidated. Insulin‐like growth factor‐I (IGF‐I) is known to be involved in airway remodelling and inflammation, while its regulatory mechanisms remain to be defined. Objective To further clarify the biological function of IL‐17F, we investigated whether IL‐17F is able to regulate the expression of IGF‐I in bronchial epithelial cells. Methods Bronchial epithelial cells were stimulated with IL‐17F in the presence or absence of T‐helper type 2 cytokines. Various kinase inhibitors were added to the culture to identify the key signalling events leading to the expression of IGF‐I, in conjunction with the use of short interfering RNAs (siRNAs) targeting mitogen‐ and stress‐activated protein kinase (MSK) 1, p90 ribosomal S6 kinase (p90RSK), and cyclic AMP response element‐binding protein (CREB). Results IL‐17F significantly induced IGF‐I gene and protein expression, and co‐stimulation with IL‐4 and IL‐13 augmented its production. MAP kinase kinase (MEK) inhibitors and the Raf1 kinase inhibitor significantly inhibited IGF‐I production, and the combination of PD98059 and Raf1 kinase inhibitor showed further inhibition. Overexpression of Raf1 and Ras dominant‐negative mutants inhibited its expression. MSK1 inhibitors significantly blocked IL17F‐induced IGF‐I expression. Moreover, transfection of the siRNAs targeting MSK1, p90RSK, and CREB blocked its expression. Conclusions In bronchial epithelial cells, IL‐17F is able to induce the expression of IGF‐I via the Raf1–MEK1/2–ERK1/2–MSK1/p90RSK–CREB pathway in vitro .