Visfatin, an adipocytokine with proinflammatory and immunomodulating properties
Visfatin, an adipocytokine with proinflammatory and immunomodulating properties
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DOI：
10.4049/jimmunol.178.3.1748
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发表时间：
2007-02-01
影响因子：
4.4
通讯作者：
Tilg, Herbert
中科院分区：
文献类型：
--
作者：
Moschen, Alexander R.;Kaser, Arthur;Tilg, Herbert
脂肪细胞因子主要是调节代谢的脂肪细胞源性细胞因子，因此是胰岛素抵抗的关键调节剂。一些脂肪细胞因子如脂联素和瘦素影响免疫和炎症功能。内脂素（前B细胞集落增强因子）是最近发现的一种新的脂肪细胞因子，通过与胰岛素受体结合影响胰岛素抵抗。在这项研究中，我们表明，重组内脂素激活人类白细胞和诱导细胞因子的产生。在CD 14（+）单核细胞中，内脂素诱导IL-1 β、TNF-α，尤其是IL-6的产生。此外，它增加了共刺激分子CD 54、CD 40和CD 80的表面表达。内脂素刺激的单核细胞显示增强的FITC-葡聚糖摄取和增强的诱导人淋巴细胞同种异体增殖反应的能力。内脂素诱导的效应涉及p38以及MEK 1途径，如通过MAPK抑制剂抑制所确定的，并且我们观察到NF-κ B的活化。在体内，内脂素在BALB/c小鼠中诱导循环IL-6。在炎症性肠病患者中，与健康对照组相比，克罗恩病和溃疡性结肠炎患者的结肠组织中内脂素的血浆水平升高，其mRNA表达显著增加。巨噬细胞、树突状细胞和结肠上皮细胞可能是内脂素的额外来源，如通过共聚焦显微镜所确定的。内脂素可被认为是一种新的促炎性脂肪细胞因子。
Adipocytokines are mainly adipocyte-derived cytokines regulating metabolism and as such are key regulators of insulin resistance. Some adipocytokines such as adiponectin and leptin affect immune and inflammatory functions. Visfatin (pre-B cell colony-enhancing factor) has recently been identified as a new adipocytokine affecting insulin resistance by binding to the insulin receptor. In this study, we show that recombinant visfatin activates human leukocytes and induces cytokine production. In CD14(+) monocytes, visfatin induces the production of IL-1 beta, TNF-alpha, and especially IL-6. Moreover, it increases the surface expression of costimulatory molecules CD54, CD40, and CD80. Visfatin-stimulated monocytes show augmented FITC-dextran uptake and an enhanced capacity to induce alloproliferative responses in human lymphocytes. Visfatin-induced effects involve p38 as well as MEK1 pathways as determined by inhibition with MAPK inhibitors and we observed activation of NF-kappa B. In vivo, visfatin induces circulating IL-6 in BALB/c mice. In patients with inflammatory bowel disease, plasma levels of visfatin are elevated and its mRNA expression is significantly increased in colonic tissue of Crohn's and ulcerative colitis patients compared with healthy controls. Macrophages, dendritic cells, and colonic epithelial cells might be additional sources of visfatin as determined by confocal microscopy. Visfatin can be considered anew proinflammatory adipocytokine.