Examinando por Autor "Dubois-Camacho, K."
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Ítem A functional IL1RL1 variant regulates corticosteroid-induced sST2 expression in ulcerative colitis(Nature Publishing Group, 2017-12) 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.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.Ítem Pannexin-1 expression in tumor cells correlates with colon cancer progression and survival(Elsevier, 2024-08) Fierro-Arenas, A.; Landskron, G.; Camhi-Vainroj, I.; Basterrechea, B.; Parada-Venegas, D.; Lobos-González, L.; Dubois-Camacho, K.; Araneda, C.; Romero, C.; Domínguez, A.; Vásquez, G.; López, F.; Alvarez, K.; González, C.; Hager, C.; Balboa, E.; Eugenin, E.; Hermoso, M.; De la Fuente, M.Aims Pannexin-1 (PANX1) is a hemichannel that releases ATP upon opening, initiating inflammation, cell proliferation, and migration. However, the role of PANX1 channels in colon cancer remains poorly understood, thus constituting the focus of this study. Main methods PANX1 mRNA expression was analyzed using multiple cancer databases. PANX1 protein expression and distribution were evaluated by immunohistochemistry on primary tumor tissue and non-tumor colonic mucosa from colon cancer patients. PANX1 inhibitors (probenecid or 10Panx) were used to assess colon cancer cell lines viability. To study the role of PANX1 in vivo, a subcutaneous xenograft model using HCT116 cells was performed in BALB/c NOD/SCID immunodeficient mice to evaluate tumor growth under PANX1 inhibition using probenecid. Key findings PANX1 mRNA was upregulated in colon cancer tissue compared to non-tumor colonic mucosa. Elevated PANX1 mRNA expression in tumors correlated with worse disease-free survival. PANX1 protein abundance was increased on tumor cells compared to epithelial cells in paired samples, in a cancer stage-dependent manner. In vitro and in vivo experiments indicated that blocking PANX1 reduced cell viability and tumor growth. Significance PANX1 can be used as a biomarker of colon cancer progression and blocking PANX1 channel opening could be used as a potential therapeutic strategy against this disease.