1,25-Dihydroxyvitamin D3 promotes a sustained LPS-induced NF-κB-dependent expression of CD55 in human monocytic THP-1 cells.
1,25-Dihydroxyvitamin D3 promotes a sustained LPS-induced NF-κB-dependent expression of CD55 in human monocytic THP-1 cells.
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DOI：
10.1371/journal.pone.0049318
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Nowicki S
中科院分区：
文献类型：
--
作者：
Izban MG;Nowicki BJ;Nowicki S
维生素D3系统通过抑制NF-κ B依赖的促炎介质表达，对单核细胞产生免疫抑制作用。CD 55是一种促进保护和抗炎特性的细胞表面补体调节蛋白，据报道是细菌内毒素LPS在单核细胞中瞬时诱导的NF-κB靶基因。在经历早产的妇女中，白色细胞上的CD 55升高（通常与细菌感染相关的病理生理学），并且不能维持CD 55与随后的早产相关。我们使用定量PCR、免疫印迹、免疫组织化学和NF-κB活化途径抑制剂检测了维生素D3信号对LPS诱导的人单核细胞THP-1细胞中CD 55表达的影响。还检查了非NF-κB靶向CD 14和CD 11 B，其分别调节细菌监测和根除。LPS使CD 55 mRNA迅速瞬时增加1.6倍。1，25-D3单独给药后48 h内不影响CD 55 mRNA表达。然而，在1，25-D3预处理的细胞中，LPS使CD 55 mRNA和蛋白表达立即和持续增加>4倍，这被NF-κB抑制剂阻断。我们的研究结果出乎意料地表明，维生素D3信号可能通过NF-κ B依赖性增加CD 55表达来促进抗炎反应。正如预期的那样，LPS或1，25-D3单独导致CD 14和CD 11b表达的持续增加。在1，25-D3预处理的细胞中，LPS差异调节蛋白质表达-CD 14（增加21倍）和CD 11b（瞬时减少2倍）-主要在转录后水平。CD 55、CD 14和CD 11b的协调时间表达将通过在病原体识别和根除期间提供针对补体介导的细胞裂解的保护而有助于抗炎反应。总的来说，维生素D3系统可能在协调宿主补体免疫系统的抗炎反应模式中发挥作用。这可能是特别重要的，当考虑到早产率高的黑人，一个人口，表现出降低循环维生素D3水平。
The vitamin D3 system imposes immunosuppressive effects on monocytic cells, in part, by inhibiting NF-κB-dependent expression of proinflammatory mediators. CD55, a cell surface complement regulatory protein that promotes protective and anti-inflammatory properties, is reportedly an NF-κB target gene transiently induced in monocytic cells by the bacterial endotoxin LPS. CD55 is elevated on white cells in women experiencing preterm labor (a pathophysiology commonly associated with bacterial infection) and failure to maintain CD55 was associated with subsequent preterm delivery. We examined the influence of vitamin D3 signaling on LPS-induced expression of CD55 in human monocytic THP-1 cells using quantitative PCR, immunoblot, immunohistochemistry, and NF-κB activation pathway inhibitors. Non-NF-κB targets CD14 and CD11b, which modulate bacterial surveillance and eradication, respectively, were also examined. LPS produced a rapid transient 1.6-fold increase in CD55 mRNA. 1,25-D3 alone did not affect CD55 mRNA expression within the first 48 h. However, in 1,25-D3 pretreated cells, LPS produced a >4-fold immediate and sustained increase in CD55 mRNA and protein expression, which was blocked by NF-κB inhibitors. Our results unexpectedly suggest that vitamin D3 signaling may promote an anti-inflammatory response through an NF-κB-dependent increase in CD55 expression. As expected, LPS or 1,25-D3 alone led to sustained increases in CD14 and CD11b expression. In 1,25-D3 pretreated cells, LPS differentially regulated protein expression - CD14 (21-fold increase) and CD11b (a transient 2-fold decrease) - principally at the posttranscriptional level. The coordinated temporal expression of CD55, CD14 and CD11b would contribute to an anti-inflammatory response by providing protection against complement-mediated cell lysis during pathogen recognition and eradication. Overall, the vitamin D3 system may play a role coordinating an anti-inflammatory response pattern of the host complement immune system. This may be particularly important when considering the high rates of preterm births in blacks, a population that exhibits reduced circulating vitamin D3 levels.
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影响因子：
5.8
作者：
Campbell, F. C.;Xu, Haibo;El-Tanani, M.;Crowe, P.;Bingham, V.
通讯作者：
Bingham, V.
DOI：
10.1084/jem.20030380
发表时间：
2003-10-06
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Lawrence DW;Bruyninckx WJ;Louis NA;Lublin DM;Stahl GL;Parkos CA;Colgan SP
通讯作者：
Colgan SP
影响因子：
12.3
作者：
Klug M;Heinz S;Gebhard C;Schwarzfischer L;Krause SW;Andreesen R;Rehli M
通讯作者：
Rehli M
影响因子：
15.3
作者：
Hmama, Z;Nandan, D;Sly, L;Knutson, K L;Herrera-Velit, P;Reiner, N E
通讯作者：
Reiner, N E
影响因子：
4.8
作者：
Garcia, Leah A.;King, Keisha K.;Artaza, Jorge N.
通讯作者：
Artaza, Jorge N.