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Please use this identifier to cite or link to this item: http://hdl.handle.net/10564/3102

Title: Interleukin-6/STAT pathway is responsible for the induction of gene expression of REG Iα, a new auto-antigen in Sjögren׳s syndrome patients, in salivary duct epithelial cells.
Other Titles: シェーグレン症候群の新規自己抗原であるREG 蛋白の唾液導管細胞における発現誘導にはIL-6/STAT 経路が重要である
Authors: Fujimura, Takanori
Fujimoto, Takashi
Itaya-Hironaka, Asako
Miyaoka, Tomoko
Yoshimoto, Kiyomi
Yamauchi, Akiyo
Sakuramoto-Tsuchida, Sumiyo
Kondo, Saori
Takeda, Maiko
Tsujinaka, Hiroki
Azuma, Masayuki
Tanaka, Yasuhito
Takasawa, Shin
Keywords: Regenerating gene
Sjögren׳s syndrome
Janus kinase
Signal transducer and activator of transcription
Issue Date: Jul-2015
Publisher: Elsevier
Citation: Biochemistry and biophysics reports Vol.2 p.69-74(2015 Jul)
Abstract: The regenerating gene, Reg, was originally isolated from a rat regenerating islet cDNA library, and its human homolog was named REG Iα. Recently, we reported that REG Iα mRNA as well as its product were overexpressed in ductal epithelial cells in the minor salivary glands of Sjögren׳s syndrome (SS) patients. This study was undertaken to elucidate the role of cytokines and the subsequent intracellular mechanism for induction of REG Iα in the salivary glands of SS patients. We prepared a reporter plasmid containing REG Iα promoter (−1190/+26) upstream of a luciferase reporter gene. The promoter plasmid was introduced by lipofection into human NS-SV-DC and rat A5 salivary ductal cells. The cells were treated with interleukin (IL)-6, IL-8, and a combination of the two. Thereafter transcriptional activity of REG Iα was measured by luciferase assay. We found that IL-6 stimulation, but not IL-8, significantly enhanced the REG Iα promoter activity in salivary ductal cells. Deletion analysis revealed that the region of −141 to −117 of the REG Iα gene was responsible for the promoter activation by IL-6, which contains a consensus sequence for signal transduction and activation of transcription (STAT). The introduction of siRNA for human STAT3 abolished IL-6-induced REG Iα transcription. These results showed that IL-6 stimulation induced REG Iα transcription through STAT3 activation and binding to the consensus sequence of REG Iα promoter in salivary ductal cells. This IL-6/STAT dependent REG Iα induction might play a role in the pathogenesis of SS.
Description: 博士(医学)・甲第641号・平成27年11月27日
Copyright © 2015 The Authors. Published by Elsevier B.V. This is an open access article under the CCBY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
URI: http://hdl.handle.net/10564/3102
ISSN: 24055808
Academic Degrees and number: 24601A641
Degree-granting date: 2015-11-27
Degree name: 博士(医学)
Degree-granting institutions: 奈良県立医科大学
Appears in Collections:2015年度

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