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- Title
Interleukin-33 induces interleukin-17 F in bronchial epithelial cells.
- Authors
Fujita, J.; Kawaguchi, M.; Kokubu, F.; Ohara, G.; Ota, K.; Huang, S.-K.; Morishima, Y.; Ishii, Y.; Satoh, H.; Sakamoto, T.; Hizawa, N.
- Abstract
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-17 F is also involved in the pathogenesis of asthma. However, the regulatory mechanisms of IL-17 F expression remain to be defined. To further indentify the role of IL-33 in asthma, we investigated the expression of IL-17 F by IL-33 in bronchial epithelial cells and its signaling mechanisms. Methods Bronchial epithelial cells were stimulated with IL-33. The levels of IL-17 F 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-17 F, in conjunction with the use of short interfering RNAs (si RNAs) targeting MSK1. Results IL-33 significantly induced IL-17 F 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 p38 MAPK and JNK. It was inhibited by the pretreatment of anti- ST2 neutralizing (blocking) Abs. MEK inhibitor significantly blocked IL-17 F production. Moreover, IL-33 phosphorylated MSK1, and MEK inhibitor diminished its phosphorylation. Finally, MSK1 inhibitors and transfection of the si RNAs targeting MSK1 significantly blocked the IL-17 F expression. Conclusions IL-33 induces IL-17 F via ST2- ERK1/2- MSK1 signaling pathway in bronchial epithelial cells. These data suggest that the IL-33/ IL-17 F axis is involved in allergic airway inflammation and may be a novel therapeutic target.
- Subjects
ASTHMA; INTERLEUKIN-33; INTERLEUKIN-17; EPITHELIAL cells; MITOGEN-activated protein kinases
- Publication
Allergy, 2012, Vol 67, Issue 6, p744
- ISSN
0105-4538
- Publication type
Article
- DOI
10.1111/j.1398-9995.2012.02825.x