Induction of insulin-like growth factor-I by interleukin-17F in bronchial epithelial cells

M. Kawaguchi, J. Fujita, F. Kokubu, G. Ohara, S. K. Huang, S. Matsukura, Y. Ishii, M. Adachi, H. Satoh, N. Hizawa

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Abstract

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.

Original languageEnglish
Pages (from-to)1036-1043
Number of pages8
JournalClinical and Experimental Allergy
Volume40
Issue number7
DOIs
Publication statusPublished - Jul 1 2010
Externally publishedYes

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Keywords

  • Bronchial epithelial cell
  • IGF-I
  • IL-17F

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Kawaguchi, M., Fujita, J., Kokubu, F., Ohara, G., Huang, S. K., Matsukura, S., Ishii, Y., Adachi, M., Satoh, H., & Hizawa, N. (2010). Induction of insulin-like growth factor-I by interleukin-17F in bronchial epithelial cells. Clinical and Experimental Allergy, 40(7), 1036-1043. https://doi.org/10.1111/j.1365-2222.2010.03527.x