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http://ir.nhri.org.tw/handle/3990099045/6451
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| Title: | Interleukin-33 induces interleukin-17F in bronchial epithelial cells |
| Authors: | Fujita, J;Kawaguchi, M;Kokubu, F;Ohara, G;Ota, K;Huang, SK;Morishima, Y;Ishii, Y;Satoh, H;Sakamoto, T;Hizawa, N |
| Contributors: | Division of Environmental Health and Occupational Medicine |
| 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-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. |
| Date: | 2012-06 |
| Relation: | Allergy. 2012 Jun;67(6):744-750. |
| Link to: | http://dx.doi.org/10.1111/j.1398-9995.2012.02825.x |
| JIF/Ranking 2023: | http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=0105-4538&DestApp=IC2JCR |
| Cited Times(WOS): | https://www.webofscience.com/wos/woscc/full-record/WOS:000303854900006 |
| Cited Times(Scopus): | http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=84861101313 |
| Appears in Collections: | [黃嘯谷] 期刊論文
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| SCP84861101313.pdf | | 400Kb | Adobe PDF | 458 | View/Open |
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