IL-31, a newly identified member of the IL-6 cytokine family, is involved in many pathological conditions, including atopic dermatitis and pruritis. In this study, we investigated how expression of IL-31 is regulated in T cells and mast cells. We observed that expression of IL-31 required a calcium signal and was dependent on the calcineurin-NFAT signaling pathway. Moreover, we found that IL-31 promoter contains a positive regulatory region that mediates calcium- and IL-4-dependent induction of the IL-31 gene and demonstrated that a change into an open chromatin conformation occurs in this region after stimulation with calcium and IL-4. Whereas IL-4 responsiveness required STAT6 binding sites, calcium responsiveness of IL-31 promoter required NFAT binding sites that bind NFATc1 and NFATc2 in vitro and in vivo. The induction of IL-31 promoter activity was impaired when these sites were mutated but was enhanced by CA-NFATc1 or STAT6 proteins and further increased synergistically by combinations of both proteins. Furthermore, the importance of STAT6 proteins was indicated by impaired, IL-4-mediated induction of IL-31 in STAT6-diminished Jurkat cells. Thus, our data demonstrate that calcium and IL-4 signals are required to mediate induction of IL-31 in Th2 cells and mast cells and that this induction appears to result from specific binding of NFAT and STAT6 proteins. Th2 mast cells calcium IL-4 Footnotes CA-NFATc1 constitutively active form of nuclear factor of activated T cell c1 ChIP chromatin immunoprecipitation CNS conserved noncoding sequence CsA cyclosporin A dnNFAT dominant-negative nuclear factor of activated T cell H3K4me3 H3 trimethyl lysine 4 mtN1–N4/S1–S3/NS mutation of NFAT site 1-4/STAT6 site 1-3/NFAT and STAT6 sites mtNS mutation of the NFAT and STAT6 sites NFAT nuclear factor of activated T cell NP-40 Nonidet P-40 PI PMA and ionomycine shRNA short hairpin RNA STAT-VT constitutively active form of STAT6 with a VT/AA mutation at amino acids 625 and 626 Received January 13, 2011. Revision received September 21, 2011. Accepted October 8, 2011. © 2012 Society for Leukocyte Biology Facebook Google+ LinkedIn Mendeley Reddit StumbleUpon Technorati Twitter What's this? « Previous | Next Article » Table of Contents This Article Published online before print November 1, 2011 , doi: 10.1189/jlb.0111020 February 2012 Journal of Leukocyte Biology vol. 91 no. 2 245-257 » Abstract Full Text Full Text (PDF) All Versions of this Article: jlb.0111020v1 91/2/245 most recent Classifications Receptors, Signal Transduction, & Genes Services Email this article to a colleague Alert me when this article is cited Alert me if a correction is posted Similar articles in this journal Similar articles in PubMed Download to citation manager Citing Articles Load citing article information Google Scholar Articles by Park, K. Articles by Kim, H. PubMed PubMed citation Articles by Park, K. Articles by Kim, H. Related Content Load related web page information Sharing Email this article to a colleague Facebook Google+ LinkedIn Mendeley Reddit StumbleUpon Technorati Twitter What's this? Current Issue February 2012, 91 (2) From the Cover Editorials: Tim-3 puts on the brakes. Editorials: T cell memory, bone marrow, and aging: the good news. Spotlight on Leading Edge Research: Tim-3 regulates pro- and anti-inflammatory cytokine expression in human CD14+ monocytes. Spotlight on Leading Edge Research: The impact of aging on memory T cell phenotype and function in the human bone marrow. Reviews: Lipid-cytokine-chemokine cascades orchestrate leukocyte recruitment in inflammation. Reviews: Non-human primate dendritic cells. Alert me to new issues of Journal of Leukocyte Biology About JLB Submit Manuscripts Instructions for Authors Information for Reviewers Editorial Board Editorial Policies Subscriptions Librarian's Resource Advertising Press Room Copyright Permissions Feedback Join SLB SLB Annual Meeting Copyright © 2012 by the Society for Leukocyte Biology Print ISSN: 0741-5400 Online ISSN: 1938-3673 var gaJsHost = (("https:" == document.location.protocol) ? "https://ssl." : "http://www."); document.write(unescape("%3Cscript src='" + gaJsHost + "google-analytics.com/ga.js' type='text/javascript'%3E%3C/script%3E")); var pageTracker = _gat._getTracker("UA-23108860-1"); pageTracker._trackPageview();

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