Human resistin is a systemic immune-derived proinflammatory cytokine targeting both leukocytes and adipocytes.
Human resistin is a systemic immune-derived proinflammatory cytokine targeting both leukocytes and adipocytes.
复制标题
DOI：
10.1371/journal.pone.0000031
复制
发表时间：
2006-12-20
期刊：
影响因子：
3.7
通讯作者：
Smith U
中科院分区：
文献类型：
--
作者：
Nagaev I;Bokarewa M;Tarkowski A;Smith U
尽管针对脂肪的研究非常深入，但人类的RETN（RETN）的特征仍不清楚且存在争议。其转录和功能的相似性与鼠骨髓特异性和CCAAT/增强子结合蛋白GAL 10（Cebpe）依赖性基因，抵抗素样γ（Retnlg），是未开发的。我们通过无偏参考和定制基因表达测定来检查人CEBPE调节途径。实时RT-PCR分析表明，缺乏的脂肪和肌肉细胞中的转录因子CEBPE和RETN的表达。相比之下，原代髓细胞样品显示协同CEBPE-RETN转录，其在炎性滑膜细胞中相对于完整的外周血单核细胞（PBMC）显著升高。小鼠Cebpe和Retnlg可预测地在巨噬细胞中表达，而Retn在脂肪细胞中丰富。恰恰相反，在一些人类白色脂肪组织（WAT）活检中观察到低且不一致的RETN转录，与体重指数、胰岛素敏感性或脂肪储存没有任何关系。然而，在这些情况下，RETN与CEBPE和白细胞特异性标记物EMR 1共同检测到，表明炎性细胞的存在及其对脂肪细胞可能的抵抗素介导的作用。事实上，在培养物中向WAT中加入人IFN诱导，如在PBMC中，炎性细胞因子IL 6、IL 8和TNF。重要的是，脂肪特异性标志物CEBPA、FABP 4和SLC 2A 4的表达没有变化，而TNF则观察到预期的抑制作用。两种细胞因子均增加了CCL 2和MMP 3的mRNA水平，这可能进一步促进WAT中的炎症。因此，CEBPE的骨髓限制性质排除了RETN在人脂肪细胞中的表达，然而，人脂肪细胞是这种先天免疫衍生的促炎细胞因子的靶向。
The characteristics of human resistin (RETN) are unclear and controversial despite intensive adipose-focused research. Its transcriptional and functional similarity with the murine myeloid-specific and CCAAT/enhancer binding protein epsilon (Cebpe)-dependent gene, resistin-like gamma (Retnlg), is unexplored. We examined the human CEBPE-regulatory pathway by unbiased reference and custom gene expression assays. Real-time RT-PCR analysis demonstrated lack of both the transcriptional factor CEBPE and RETN expression in adipose and muscle cells. In contrast, primary myelocytic samples revealed a concerted CEBPE-RETN transcription that was significantly elevated in inflammatory synoviocytes relative to intact peripheral blood mononuclear cells (PBMC). Mouse Cebpe and Retnlg were predictably expressed in macrophages, whereas Retn was abundant in adipocytes. Quite the opposite, a low and inconsistent RETN transcription was seen in some human white adipose tissue (WAT) biopsies without any relationship to body mass index, insulin sensitivity, or fat depot. However, in these cases, RETN was co-detected with CEBPE and the leukocyte-specific marker, EMR1, indicating the presence of inflammatory cells and their possible resistin-mediated effect on adipocytes. Indeed, addition of human resistin to WAT in culture induced, like in PBMC, the inflammatory cytokines IL6, IL8 and TNF. Importantly, the expression of the adipose-specific markers CEBPA, FABP4 and SLC2A4 was unchanged, while the expected inhibitory effect was seen with TNF. Both cytokines increased the mRNA level of CCL2 and MMP3, which may further promote inflammation in WAT. Thus, the myeloid-restricted nature of CEBPE precludes the expression of RETN in human adipocytes which, however, are targeted by this innate immune-derived proinflammatory cytokine.
登录
查看更多内容
影响因子：
11.4
作者：
Holcomb, IN;Kabakoff, RC;Hébert, CC
通讯作者：
Hébert, CC
影响因子：
5.8
作者：
McTernan, PG;Fisher, FM;Kumar, S
通讯作者：
Kumar, S
影响因子：
2.1
作者：
Dai, MH;Xia, T;Yang, ZQ
通讯作者：
Yang, ZQ
影响因子：
37.8
作者：
Mazurek, T;Zhang, LF;Shi, Y
通讯作者：
Shi, Y
影响因子：
9.3
作者：
Baker, Adam R.;da Silva, Nancy F.;Quinn, David W.;Harte, Alison L.;Pagano, Domenico;Bonser, Robert S.;Kumar, Sudhesh;McTernan, Philip G.
通讯作者：
McTernan, Philip G.