IL-33 promotes IL-10 production in macrophages: a role for IL-33 in macrophage foam cell formation.
IL-33 promotes IL-10 production in macrophages: a role for IL-33 in macrophage foam cell formation.
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IL-33 促进巨噬细胞中 IL-10 的产生：IL-33 在巨噬细胞泡沫细胞形成中的作用
DOI：
10.1038/emm.2017.183
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发表时间：
2017-11-03
影响因子：
12.8
通讯作者：
Wang JF
中科院分区：
文献类型：
--
作者：
Zhang HF;Wu MX;Lin YQ;Xie SL;Huang TC;Liu PM;Nie RQ;Meng QQ;Luo NS;Chen YX;Wang JF
我们评估了IL-10在IL-33介导的巨噬细胞源性泡沫细胞（MFC）胆固醇降低中的作用以及IL-33上调IL-10的机制。测定冠心病患者血清IL-33和IL-10水平。测定IL-33对MFC内胆固醇水平、IL-10、ABCA 1和CD 36表达、ERK 1/2、Sp1、STAT 3和STAT 4活化以及IL-10启动子活性的影响。使用生物信息学分析和位点特异性诱变鉴定核心序列。血清IL-33水平与IL-10水平呈正相关。IL-33降低细胞胆固醇水平，上调IL-10和ABCA 1，但对CD 36表达无影响。siRNA-IL-10部分消除了IL-33引起的细胞胆固醇降低和ABCA 1升高，但没有逆转降低的CD 36水平。IL-33增加IL-10 mRNA的产生，但对其稳定性影响不大。IL-33诱导ERK 1/2磷酸化，并增加由IL-10启动子驱动的荧光素酶表达，在转录起始位点5′侧翼的− 2000至− 1752 bp片段内表达最高;这些作用被U 0126抵消。IL-33激活了Sp1、STAT 3和STAT 4，但在上述片段中仅预测了STAT 3结合位点。预测的STAT 3结合位点的定点突变（CTGCTTCCTGGCAGCAGAA→ CTGCCTGGCAGCAGAA）降低了荧光素酶活性，STAT 3抑制剂阻断了IL-33对IL-10表达的调节作用。染色质免疫沉淀（CHIP）证实了STAT 3结合序列位于− 1997至− 1700和− 1091至− 811 bp基因座区域内。IL-33通过激活ERK 1/2和STAT 3增加MFC中IL-10的表达，随后促进IL-10的转录，从而有助于IL-33对MFC的有益作用。
We evaluated the role of IL-10-in IL-33-mediated cholesterol reduction in macrophage-derived foam cells (MFCs) and the mechanism by which IL-33 upregulates IL-10. Serum IL-33 and IL-10 levels in coronary artery disease patients were measured. The effects of IL-33 on intra-MFC cholesterol level, IL-10, ABCA1 and CD36 expression, ERK 1/2, Sp1, STAT3 and STAT4 activation, and IL-10 promoter activity were determined. Core sequences were identified using bioinformatic analysis and site-specific mutagenesis. The serum IL-33 levels positively correlated with those of IL-10. IL-33 decreased cellular cholesterol level and upregulated IL-10 and ABCA1 but had no effect on CD36 expression. siRNA-IL-10 partially abolished cellular cholesterol reduction and ABCA1 elevation by IL-33 but did not reverse the decreased CD36 levels. IL-33 increased IL-10 mRNA production but had little effect on its stability. IL-33 induced ERK 1/2 phosphorylation and increased the luciferase expression driven by the IL-10 promoter, with the highest extent within the− 2000 to− 1752 bp segment of the 5′-flank of the transcription start site; these effects were counteracted by U0126. IL-33 activated Sp1, STAT3 and STAT4, but only the STAT3 binding site was predicted in the above segment. Site-directed mutagenesis of the predicted STAT3-binding sites (CTGCTTCCTGGCAGCAGAA→ CTGCCTGGCAGCAGAA) reduced luciferase activity, and a STAT3 inhibitor blocked the regulatory effects of IL-33 on IL-10 expression. Chromatin immunoprecipitation (CHIP) confirmed the STAT3-binding sequences within the− 1997 to− 1700 and− 1091 to− 811 bp locus regions. IL-33 increased IL-10 expression in MFCs via activating ERK 1/2 and STAT3, which subsequently promoted IL-10 transcription and thus contributed to the beneficial effects of IL-33 on MFCs.
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DOI：
10.1016/j.bbrc.2006.04.038
发表时间：
2006-06-16
影响因子：
3.1
作者：
Rosenblat, Mira;Oren, Roni;Aviram, Michael
通讯作者：
Aviram, Michael
影响因子：
12.8
作者：
Hong GH;Kwon HS;Lee KY;Ha EH;Moon KA;Kim SW;Oh W;Kim TB;Moon HB;Cho YS
通讯作者：
Cho YS
影响因子：
4.8
作者：
Ma, W;Lim, W;Kumar, A
通讯作者：
Kumar, A
影响因子：
5.4
作者：
Liu, Bi-Sheng;Cao, Yonghao;Toes, Rene E. M.
通讯作者：
Toes, Rene E. M.
影响因子：
4.4
作者：
Yang, Ziyan;Mosser, David M.;Zhang, Xia
通讯作者：
Zhang, Xia