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Vitamin D Inhibits Monocyte/Macrophage Proinflammatory Cytokine Production by Targeting MAPK Phosphatase-1
Open accessAbstract
It is estimated that 1 billion people around the world are vitamin D deficient. Vitamin D deficiency has been linked to various inflammatory diseases. However, the mechanism by which vitamin D reduces inflammation remains poorly understood. In this study, we investigated the inhibitory effects of physiologic levels of vitamin D on LPS-stimulated inflammatory response in human blood monocytes and explored potential mechanisms of vitamin D action. We observed that two forms of the vitamin D, 1,25(OH)2D3, and 25(OH)D3, dose dependently inhibited LPS-induced p38 phosphorylation at physiologic concentrations, IL-6 and TNF-α production by human monocytes. Upon vitamin D treatment, the expression of MAPK phosphatase-1 (MKP-1) was significantly upregulated in human monocytes and murine bone marrow-derived macrophages (BMM). Increased binding of the vitamin D receptor and increased histone H4 acetylation at the identified vitamin D response element of the murine and human MKP-1 promoters were demonstrated. Moreover, in BMM from MKP1−/− mice, the inhibition of LPS-induced p38 phosphorylation by vitamin D was completely abolished. Vitamin D inhibition of LPS-induced IL-6 and TNF-α production by BMM from MKP-1−/− mice was significantly reduced as compared with wild-type mice. In conclusion, this study identified the upregulation of MKP-1 by vitamin D as a novel pathway by which vitamin D inhibits LPS-induced p38 activation and cytokine production in monocytes/macrophages.
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Metadata
- Authors
- Zhang, Y., Leung, D. Y. M., Richers, B. N., Liu, Y., Remigio, L. K., Riches, D. W., & Goleva, E.
- Venue
- The Journal of Immunology
- Publisher
- Oxford University Press (OUP)
- Published
- 2012-03-01
- Volume
- 188
- Issue
- 5
- Pages
- 2127-2135
- ISSN
- 0022-1767 (ISSN-L)
- 1550-6606
- OpenAlex
- W2157243060
- Cited by
- 878
- References
- 11
- FWCI
- 32.21
- Type
- journal article
- Language
- en
- Open access
- green
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