PT  - JOURNAL ARTICLE
AU  - Zhang, Yong
AU  - Leung, Donald Y. M.
AU  - Richers, Brittany N.
AU  - Liu, Yusen
AU  - Remigio, Linda K.
AU  - Riches, David W.
AU  - Goleva, Elena
TI  - Vitamin D Inhibits Monocyte/Macrophage Proinflammatory Cytokine Production by Targeting MAPK Phosphatase-1
AID  - 10.4049/jimmunol.1102412
DP  - 2012 Mar 01
TA  - The Journal of Immunology
PG  - 2127--2135
VI  - 188
IP  - 5
4099  - http://www.jimmunol.org/content/188/5/2127.short
4100  - http://www.jimmunol.org/content/188/5/2127.full
SO  - J. Immunol.2012 Mar 01; 188
AB  - 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.