Role of proinflammatory cytokines on expression of vitamin D metabolism and target genes in colon cancer cells
Open accessAbstract
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'.
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Children in Molloy et al. were suffering from some form of acute inflammation, which potentially had an effect on 25(OH)D levels.
“Children were suffering from some form of acute inflammation, which potentially had an effect on 25(OH)D levels [120,121].”
From Vitamin D and Autism Spectrum Disorder: A Literature Review (2016) · cites this paper as [121]
Inflammation, gastrointestinal issues, antiepileptic drugs and genetics are among factors affecting vitamin D metabolism or absorption.
“Inflammation [120,121], gastrointestinal issues [123,124], antiepileptic drugs [125] and genetics are among these factors.”
From Vitamin D and Autism Spectrum Disorder: A Literature Review (2016) · cites this paper as [121]
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Vitamin D and Autism Spectrum Disorder: A Literature Review
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- Authors
- Hummel, D. M., Fetahu, I. S., Gröschel, C., Manhardt, T., & Kállay, E.
- Affiliations
- Medical University of Vienna (AT)
- ORCID
- Fetahu, Irfete S.
- Venue
- The Journal of Steroid Biochemistry and Molecular Biology
- Publisher
- Elsevier BV
- Published
- 2014-10
- Volume
- 144
- Pages
- 91-95
- ISSN
- 0960-0760 (ISSN-L)
- PMC
- PMC4138205
- OpenAlex
- W2043201997
- Cited by
- 68
- References
- 33
- Citations by year
- 2026: 6 · 2025: 5 · 2024: 4 · 2023: 8 · 2022: 3 · 2021: 10 · 2020: 5 · 2019: 6 · 2018: 7 · 2017: 1 · 2016: 7 · 2015: 3 · 2014: 3
- FWCI
- 0.64
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- The Journal of Steroid Biochemistry and Molecular Biology (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- Austrian Science Fund
- EU Marie Curie ITN
- Topics
- Health Sciences › Medicine › Pathology and Forensic Medicine › Vitamin D Research Studies
- Health Sciences › Medicine › Pharmacology › Inflammatory mediators and NSAID effects
- Health Sciences › Medicine › Nephrology › Parathyroid Disorders and Treatments
- Keywords
- vitamin D metabolism, interleukin-6, TNF-α, inflammatory cytokines, 1,25-dihydroxyvitamin D3, CYP27B1, CYP24A1, cyclooxygenase-2, 15-hydroxyprostaglandin dehydrogenase, prostaglandin E2, TRPV6, colorectal cancer, inflammatory bowel disease, colorectal carcinogenesis, colonic epithelial cells
- MeSH terms
- Animals, Colonic Neoplasms, Humans, Vitamin D, 25-Hydroxyvitamin D3 1-alpha-Hydroxylase, Calcium Channels, Gene Expression Regulation, Neoplastic, Cytokines, Inflammation Mediators, Mice, Cyclooxygenase 2
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