title: Role of proinflammatory cytokines on expression of vitamin D metabolism and target genes in colon cancer cells.
abstract: Interleukin 6 (IL-6) and tumor necrosis factor alpha (TNFα) are proinflammatory cytokines that play a critical role in inflammatory bowel disease, as well as in colorectal tumorigenesis. We hypothesize that these cytokines modulate the expression and thus activity of the vitamin D system in colonic epithelial cells. We treated the colon cancer cell line COGA-1A for 6, 12, and 24h with 1,25-dihydroxyvitamin D3 (1,25-D3), IL-6, TNFα, and with combinations of these compounds. Using quantitative RT-PCR, we analyzed mRNA expression of genes activating and catabolizing 1,25-D3 (1α-hydroxylase (CYP27B1), 24-hydroxylase (CYP24A1)), expression of several vitamin D target genes, as well as expression of cyclooxygenase 2 (COX-2) and 15-hydroxyprostaglandin dehydrogenase. As expected, treatment with 1,25-D3 resulted in an upregulation of CYP24A1, whereas expression of CYP27B1 was not affected. Treatment with TNFα and IL-6 led to decreased expression of the vitamin D activating enzyme CYP27B1. The strong inflammatory property of TNFα was mirrored by its activation of COX-2 and inhibition of prostaglandin E2 (PGE2) catabolism. Interestingly, expression of the calcium ion channel TRPV6 was markedly decreased by TNFα. We conclude from these results that the presence of proinflammatory cytokines might impair activation of 1,25-D3, limiting its anti-inflammatory action. This article is part of a Special Issue entitled '16th Vitamin D Workshop'.
authors.affiliation: Department of Pathophysiology and Allergy Research, Medical University of Vienna, Währinger Gürtel 18-20, 1090 Vienna, Austria. Electronic address: doris.hummel@meduniwien.ac.at.
authors.forename: Doris M
authors.initials: DM
authors.lastname: Hummel
authors.affiliation: Department of Pathophysiology and Allergy Research, Medical University of Vienna, Währinger Gürtel 18-20, 1090 Vienna, Austria. Electronic address: irfete.fetahu@meduniwien.ac.at.
authors.forename: Irfete S
authors.initials: IS
authors.lastname: Fetahu
authors.affiliation: Department of Pathophysiology and Allergy Research, Medical University of Vienna, Währinger Gürtel 18-20, 1090 Vienna, Austria. Electronic address: charlotte.groeschel@meduniwien.ac.at.
authors.forename: Charlotte
authors.initials: C
authors.lastname: Gröschel
authors.affiliation: Department of Pathophysiology and Allergy Research, Medical University of Vienna, Währinger Gürtel 18-20, 1090 Vienna, Austria. Electronic address: teresa.manhardt@meduniwien.ac.at.
authors.forename: Teresa
authors.initials: T
authors.lastname: Manhardt
authors.affiliation: Department of Pathophysiology and Allergy Research, Medical University of Vienna, Währinger Gürtel 18-20, 1090 Vienna, Austria. Electronic address: enikoe.kallay@meduniwien.ac.at.
authors.forename: Enikő
authors.initials: E
authors.lastname: Kállay
mesh_terms: D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase / Q000235:genetics / Q000378:metabolism; D000818:Animals; D015220:Calcium Channels / Q000235:genetics / Q000378:metabolism; D003110:Colonic Neoplasms / Q000235:genetics / Q000378:metabolism*; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism; D016207:Cytokines / Q000494:pharmacology*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D018836:Inflammation Mediators / Q000494:pharmacology*; D051379:Mice; D014807:Vitamin D / Q000378:metabolism*
chemical_list: D015220:Calcium Channels; D016207:Cytokines; D018836:Inflammation Mediators; D014807:Vitamin D; D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase; D051546:Cyclooxygenase 2
keywords: CYP24A1; IL-6; Inflammation; TNFα; TRPV6; Vitamin D