A functional IL1RL1 variant regulates corticosteroid-induced sST2 expression in ulcerative colitis

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dc.contributor.authorDíaz-Jiménez, D.
dc.contributor.authorNúñez, L.
dc.contributor.authorDe La Fuente, M.
dc.contributor.authorDubois-Camacho, K.
dc.contributor.authorSepúlveda, H.
dc.contributor.authorMontecino, M.
dc.contributor.authorTorres-Riquelme, A.
dc.contributor.authorGarcía-González, P.
dc.contributor.authorChnaiderman, J.
dc.contributor.authorVossenkamper, A.
dc.contributor.authorMacDonald, T.T.
dc.contributor.authorSimian, D.
dc.contributor.authorGonzález, M.
dc.contributor.authorCidlowski, J.A.
dc.contributor.authorQuera, R.
dc.contributor.authorHermoso, M.A.
dc.date.accessioned2018-02-01T19:13:47Z
dc.date.available2018-02-01T19:13:47Z
dc.date.issued2017-12
dc.descriptionIndexación: Web of Science; Scopus.es_CL
dc.description.abstractThe 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.es_CL
dc.description.urihttps://www.nature.com/articles/s41598-017-10465-0
dc.identifier.citationScientific Reports. Volume 7, Issue 1, 1 December 2017, Article number 10180es_CL
dc.identifier.issn2045-2322
dc.identifier.otherDOI: 10.1038/s41598-017-10465-0
dc.identifier.urihttp://repositorio.unab.cl/xmlui/handle/ria/5239
dc.language.isoenes_CL
dc.publisherNature Publishing Groupes_CL
dc.subjectINFLAMMATORY-BOWEL-DISEASEes_CL
dc.subjectHUMAN GLUCOCORTICOID RECEPTORes_CL
dc.subjectMAST-CELLSes_CL
dc.subjectCROHNS-DISEASEes_CL
dc.subjectSUSCEPTIBILITY LOCIes_CL
dc.subjectSOLUBLE ST2es_CL
dc.subjectBARRIER FUNCTIONes_CL
dc.subjectPROMOTER USAGEes_CL
dc.subjectDNA-BINDINGes_CL
dc.subjectIN-VIVOes_CL
dc.titleA functional IL1RL1 variant regulates corticosteroid-induced sST2 expression in ulcerative colitises_CL
dc.typeArtículoes_CL
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