國家衛生研究院 NHRI:Item 3990099045/8607
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    题名: IL-9 induces IL-8 production via STIM1 activation and ERK phosphorylation in epidermal keratinocytes: A plausible mechanism of IL-9R in atopic dermatitis
    作者: Hong, CH;Chang, KL;Wang, HJ;Yu, HS;Lee, CH
    贡献者: National Environmental Health Research Center
    摘要: Background: IL-9 and its receptor play important roles in the pathogenesis of asthma. Its role in atopic dermatitis (AD) was examined in just a few studies, including nucleotide polymorphisms, increased transcriptional levels of IL-9 and IL-9R in diseased skin, and an association of blood IL-9 levels with clinical severity. Objective: Little was known about the pathophysiological regulation of IL-9/IL-9R in AD skin. We asked whether IL-9R was expressed in epidermal keratinocytes; if so, what the functional outcome, cytokine production, and signaling pathway of IL-9/IL-9R in keratinocytes are. Methods: We measured and compared the expression of IL-9R in skin from AD patients and controls by immunofluorescence. We also performed in vitro studies on the IL-9-treated primary keratinocytes, including flow cytometry for IL-9R expressions, Western blotting for mTOR, S6K, ERK, p38, and STAT3 activations, ELISA for cytokine levels, and immunofluorescence for STIM1. Results: We found that IL-9R was indeed expressed in keratinocytes but not in fibroblasts. Its expression in keratinocytes was enhanced by IL-4 but not by TGF-beta1. IL-9 induced a moderate production of IL-8 but not CXCL16, CCL22, TSLP, nor IL-33. IL-9 induced formation of STIM1-puncta. IL-9 induced ERK phosphorylation both dose- and time-dependently, but not mTOR, S6K, p38, or STAT3. Pretreatment with U0126 (ERK inhibitor) but not rapamycin (mTOR inhibitor) abrogated the IL-9-mediated IL-8 production. Blockage of STIM1 with BTP2 or SKF96265 abrogated ERK phosphorylation and IL-8 production induced by IL-9. Conclusion: This study represents the first to show the regulation of the IL-9-STIM1-ERK-IL-8 axis in keratinocyte, and how the axis might play an important role in the pathophysiology of AD.
    日期: 2015-06
    關聯: Journal of Dermatological Science. 2015 Jun;78(3):206-214.
    Link to: http://dx.doi.org/10.1016/j.jdermsci.2015.03.004
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=0923-1811&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000355021900006
    Cited Times(Scopus): http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=84929050707
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