Interleukin-33 induces interleukin-17F in bronchial epithelial cells

J. Fujita, M. Kawaguchi, F. Kokubu, G. Ohara, K. Ota, S. K. Huang, Y. Morishima, Y. Ishii, H. Satoh, T. Sakamoto, N. Hizawa

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41 Citations (Scopus)


Background IL-33 is clearly expressed in the airway of patients with asthma, but its role in asthma has not yet been fully understood. IL-17F is also involved in the pathogenesis of asthma. However, the regulatory mechanisms of IL-17F expression remain to be defined. To further indentify the role of IL-33 in asthma, we investigated the expression of IL-17F by IL-33 in bronchial epithelial cells and its signaling mechanisms. Methods Bronchial epithelial cells were stimulated with IL-33. The levels of IL-17F expression were analyzed using real-time PCR and ELISA. Next, the involvement of ST2, MAP kinases, and mitogen- and stress-activated protein kinase1 (MSK1) was determined by Western blot analyses. Various kinase inhibitors and anti-ST2 neutralizing Abs were added to the culture to identify the key signaling events leading to the expression of IL-17F, in conjunction with the use of short interfering RNAs (siRNAs) targeting MSK1. Results IL-33 significantly induced IL-17F gene and protein expression. The receptor for IL-33, ST2, was expressed in bronchial epithelial cells. Among MAP kinases, IL-33 phosphorylated ERK1/2, but not p38MAPK and JNK. It was inhibited by the pretreatment of anti-ST2 neutralizing (blocking) Abs. MEK inhibitor significantly blocked IL-17F production. Moreover, IL-33 phosphorylated MSK1, and MEK inhibitor diminished its phosphorylation. Finally, MSK1 inhibitors and transfection of the siRNAs targeting MSK1 significantly blocked the IL-17F expression. Conclusions IL-33 induces IL-17F via ST2-ERK1/2-MSK1 signaling pathway in bronchial epithelial cells. These data suggest that the IL-33/IL-17F axis is involved in allergic airway inflammation and may be a novel therapeutic target.

Original languageEnglish
Pages (from-to)744-750
Number of pages7
JournalAllergy: European Journal of Allergy and Clinical Immunology
Issue number6
Publication statusPublished - Jun 2012


  • IL-17F
  • IL-33
  • bronchial epithelial cell

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology


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