Vitamin D inhibits monocyte/macrophage proinflammatory cytokine production by targeting MAPK phosphatase-1.
Vitamin D inhibits monocyte/macrophage proinflammatory cytokine production by targeting MAPK phosphatase-1.
复制标题
DOI：
10.4049/jimmunol.1102412
复制
发表时间：
2012-03-01
期刊：
影响因子：
--
通讯作者：
Goleva E
中科院分区：
文献类型：
--
作者：
Zhang Y;Leung DY;Richers BN;Liu Y;Remigio LK;Riches DW;Goleva E
据估计，全世界有10亿人缺乏维生素D。维生素D缺乏与各种炎症性疾病有关。然而，维生素D减少炎症的机制仍然知之甚少。在这项研究中，我们研究了生理水平的维生素D对脂多糖（LPS）刺激的人血单核细胞炎症反应的抑制作用，并探讨了维生素D作用的潜在机制。我们观察到两种形式的维生素D，1，25（OH）2D 3和25（OH）D3，在生理浓度下剂量依赖性地抑制LPS诱导的p38磷酸化，抑制人单核细胞产生IL-6和TNF-α。维生素D治疗后，人单核细胞和小鼠骨髓源性巨噬细胞（BMM）中丝裂原活化蛋白激酶磷酸酶-1（MKP-1）的表达显著上调。证明了在鼠和人MKP-1启动子的鉴定的维生素D反应元件处维生素D受体的结合增加和组蛋白H4乙酰化增加。此外，在来自MKP 1 −/−小鼠的BMM中，维生素D对LPS诱导的p38磷酸化的抑制完全消除。与野生型小鼠相比，维生素D对LPS诱导的MKP-1−/−小鼠BMM产生IL-6和TNF-α的抑制作用显著降低。总之，本研究确定维生素D上调MKP-1是一种新的途径，维生素D通过该途径抑制单核细胞/巨噬细胞中LPS诱导的p38活化和细胞因子产生。
It is estimated that one 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 lipopolysaccharide (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 mitogen-activated protein kinase 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 to 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.
登录
查看更多内容
影响因子：
56.9
作者：
Liu, PT;Stenger, S;Modlin, RL
通讯作者：
Modlin, RL
DOI：
10.1016/j.jsbmb.2006.12.078
发表时间：
2007-03-01
影响因子：
4.1
作者：
Hewison, Martin;Burke, Fiona;Adams, John S.
通讯作者：
Adams, John S.
影响因子：
4.8
作者：
Meyer, Mark B.;Goetsch, Paul D.;Pike, J. Wesley
通讯作者：
Pike, J. Wesley
影响因子：
4.4
作者：
Chen, PL;Li, J;Liu, YS
通讯作者：
Liu, YS
影响因子：
6.2
作者：
Kim, S;Shevde, NK;Pike, JW
通讯作者：
Pike, JW