Díaz-Jiménez, D.Núñez, L.De La Fuente, M.Dubois-Camacho, K.Sepúlveda, H.Montecino, M.Torres-Riquelme, A.García-González, P.Chnaiderman, J.Vossenkamper, A.MacDonald, T.T.Simian, D.González, M.Cidlowski, J.A.Quera, R.Hermoso, M.A.2018-02-012018-02-012017-12Scientific Reports. Volume 7, Issue 1, 1 December 2017, Article number 101802045-2322DOI: 10.1038/s41598-017-10465-0http://repositorio.unab.cl/xmlui/handle/ria/5239Indexación: Web of Science; Scopus.The ST2/IL33 signalling pathway has been associated with ulcerative colitis (UC). ST2, encoded by the IL1RL1 gene, is expressed as both a membrane-anchored receptor (ST2L) activated by IL33 and as a soluble receptor (sST2) with anti-inflammatory properties. In UC patients, sST2 is further increased by corticosteroid treatment; however, the glucocorticoid-mediated molecular regulation remains unknown. We therefore tested whether genetic variants in the IL1RL1 distal promoter are involved in UC and affect glucocorticoid-mediated ST2 expression. Serum ST2 levels and genetic variants in the IL1RL1 distal promoter were examined by ELISA and PCR sequencing in UC patients receiving corticosteroids. Glucocorticoid-mediated ST2 production was evaluated in intestinal mucosa cultures. Molecular regulation of glucocorticoid-mediated ST2 was assessed by RT-qPCR, ChIP assay and luciferase reporter assay. Dexamethasone effect on ST2 transcript expression was analyzed in leukocytes and related to IL1RL1 variants. Sequencing of a distal IL1RL1 promoter region demonstrated that SNPs rs6543115(C) and rs6543116(A) are associated with increased sST2 in UC patients on corticosteroids. Dexamethasone up-regulated sST2 transcription through interaction with the glucocorticoid-response element (GRE) carrying rs6543115(C) variant. Our data indicate that IL1RL1 SNPs rs6543115(C) confer susceptibility to UC and is contained in the GRE, which may modulate glucocorticoid-induced sST2 expression.enINFLAMMATORY-BOWEL-DISEASEHUMAN GLUCOCORTICOID RECEPTORMAST-CELLSCROHNS-DISEASESUSCEPTIBILITY LOCISOLUBLE ST2BARRIER FUNCTIONPROMOTER USAGEDNA-BINDINGIN-VIVOArtículo