1,25-Dihydroxyvitamin D3 inhibits the cytokine-induced secretion of MCP-1 and reduces monocyte recruitment by human preadipocytes.
1,25-Dihydroxyvitamin D3 inhibits the cytokine-induced secretion of MCP-1 and reduces monocyte recruitment by human preadipocytes.
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1,25-DiHydroxyvitamin D3 抑制细胞因子诱导的 MCP-1 分泌，并减少人类前脂肪细胞对单核细胞的募集。
DOI：
10.1038/ijo.2012.53
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发表时间：
2013-03
影响因子：
4.9
通讯作者：
Bing, C.
中科院分区：
文献类型：
--
作者：
Gao, D.;Trayhurn, P.;Bing, C.
肥胖期间的脂肪组织扩张与低度炎症状态和巨噬细胞浸润的增加有关，巨噬细胞浸润易导致胰岛素抵抗和血管功能障碍。越来越多的证据表明，维生素D3具有免疫调节作用，脂肪组织可能是维生素D3作用的靶点。前脂肪细胞是脂肪组织中的主要细胞类型之一，积极参与炎症过程。本研究调查了活性形式的维生素D3（1，25（OH）2D 3）是否影响促炎趋化因子/细胞因子的产生以及人前脂肪细胞对单核细胞的募集。MCP-1、IL-8和IL-6的分泌水平在前脂肪细胞中显著高于分化的脂肪细胞，表明前脂肪细胞可能是促炎介质的主要来源。细胞因子谱分析显示，1，25（OH）2D 3（10 nM）显著降低前脂肪细胞释放MCP-1、IL-6和IL-8。NFκB信号通路的参与通过1，25（OH）2D 3上调前体脂肪细胞中IκBα蛋白丰度来显示。此外，1，25（OH）2D 3能够减少THP-1单核细胞的迁移。用促炎刺激物，包括巨噬细胞条件（MC）培养基、TNFα和IL-1β处理，导致前脂肪细胞释放MCP-1和IL-6的蛋白质显著增加。用1，25（OH）2D 3（10 nM和100 nM）预处理可显著降低MC培养基、TNFα和IL-1β对MCP-1表达和蛋白释放的刺激作用，但对IL-6刺激释放的作用较弱。这些结果表明，1，25（OH）2D 3减少前脂肪细胞产生MCP-1和其他促炎介质，并减少单核细胞迁移。因此，维生素D3可以通过破坏巨噬细胞募集的有害循环来防止脂肪组织炎症。
Adipose tissue expansion during obesity is associated with a state of low-grade inflammation and an increase in macrophage infiltration, which predisposes to insulin resistance and vascular malfunction. Growing evidence suggests that vitamin D3 has immunoregulatory effects and adipose tissue could be a target for vitamin D3 action. Preadipocytes, one of the major cell types in adipose tissue, are actively involved in inflammatory processes. This study investigated whether the active form of vitamin D3 (1,25(OH)2D3) affects the production of proinflammatory chemokines/cytokines and the monocyte recruitment by human preadipocytes. The secretion levels of MCP-1, IL-8 and IL-6 were significantly higher in preadipocytes than in differentiated adipocytes, suggesting that preadipocytes could be a major source of proinflammatory mediators. Cytokine profile analysis revealed that 1,25(OH)2D3 (10 nM) markedly reduced the release of MCP-1, IL-6 and IL-8 by preadipocytes. The involvement of NFκB signaling was shown by the upregulation of IκBα protein abundance by 1,25(OH)2D3 in preadipocytes. In addition, 1,25(OH)2D3 was able to decrease the migration of THP-1 monocytes. Treatment with proinflammatory stimuli, including macrophage conditioned (MC) medium, TNFα and IL-1β, led to a marked increase in protein release of MCP-1 and IL-6 by preadipocytes. Pretreatment with 1,25(OH)2D3 (10 nM and 100 nM) significantly decreased the stimulatory effects of MC medium, TNFα and IL-1β on MCP-1 expression and protein release, although the effect on stimulated release of IL-6 was less potent. These results demonstrate that 1,25(OH)2D3 decreases the production of MCP-1 and other proinflammatory mediators by preadipocytes and reduces monocyte migration. Thus, vitamin D3 may protect against adipose tissue inflammation by disrupting the deleterious cycle of macrophage recruitment.
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影响因子：
4
作者：
Ching, Stephen;Kashinkunti, Soumya;Niehaus, Matthew D.;Zinser, Glendon M.
通讯作者：
Zinser, Glendon M.
影响因子：
4.6
作者：
Fain JN
通讯作者：
Fain JN
影响因子：
7.7
作者：
Lumeng, Carey N.;DeYoung, Stephanie M.;Saltiel, Alan R.
通讯作者：
Saltiel, Alan R.
影响因子：
4.1
作者：
Gao, D.;Trayhurn, P.;Bing, C.
通讯作者：
Bing, C.
影响因子：
5.1
作者：
Giulietti, Annapaula;van Etten, Evelyne;Mathieu, Chantal
通讯作者：
Mathieu, Chantal