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

作者：Diaz Jimenez David; Nunez Lucia; De la Fuente Marjorie; Dubois Camacho Karen; Sepulveda Hugo; Montecino Martin; Torres Riquelme Alejandro; Garcia Gonzalez Paulina; Chnaiderman Jonas; Vossenkamper Anna; MacDonald Thomas T; Simian Daniela; Gonzalez Maria Julieta; Cidlowski John A; Quera Rodrigo^*; Hermoso Marcela A^*

来源：Scientific Reports, 2017, 7(1): 10180.

DOI：10.1038/s41598-017-10465-0

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 rs6543

• 出版日期2017-8-31
• 单位NIH