Stimulation of NGF expression and secretion in 3T3-L1 adipocytes by prostaglandins PGD2, PGJ2, and Δ12-PGJ2
Stimulation of NGF expression and secretion in 3T3-L1 adipocytes by prostaglandins PGD2, PGJ2, and Δ12-PGJ2
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DOI：
10.1152/ajpendo.00008.2005
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发表时间：
2005-07-01
影响因子：
5.1
通讯作者：
Trayhurn, P
中科院分区：
文献类型：
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作者：
Bulló, M;Peeraully, MR;Trayhurn, P
神经生长因子(NGF)最近被证明是由白色脂肪细胞分泌的，其产生受到促炎细胞因子肿瘤坏死因子-α的强烈刺激。在这项研究中，我们使用3T3-L1细胞检测了一系列前列腺素和其他炎症相关因素是否也刺激脂肪细胞NGF的表达和分泌。尽管IL-1β、IL-10和IL-18均可引起3T3-L1脂肪细胞NGF mRNA水平的轻微下降，但这些细胞因子对NGF的分泌无明显影响。脂联素和前列腺素PGE(2)、PGF(2α)和PGI(2)也使NGF的表达和/或分泌略有减少。与之形成鲜明对比的是，前列腺素PGD(2)可显著增加NGF的表达和分泌(最高可达20-40倍)，且呈剂量依赖性。PGD(2)代谢产物PGJ(2)和Delta(12)-PGJ(2)也导致NGF产量大幅增加(最高可达30倍)。PGJ(2)的进一步代谢产物15-脱氧-Delta(12，14)-PGJ(2)是一种过氧化体增殖物激活的受体-γ激动剂，矛盾地导致NGF mRNA水平略有增加，但NGF分泌下降。PGD(2)和PGJ(2)在加入后4h均可诱导NGF基因表达显著增加。结论：PGD(2)和J系列前列腺素PGJ(2)和Delta(12)-PGJ(2)在调节白色脂肪细胞产生NGF中起重要作用。这些结果支持了NGF是白色脂肪组织中重要的炎症反应蛋白和靶源性神经营养因子的观点。
Nerve growth factor (NGF) has recently been shown to be secreted from white adipocytes, its production being strongly stimulated by the proinflammatory cytokine tumor necrosis factor-alpha. In this study, we have examined whether a series of prostaglandins and other inflammation-related factors also stimulate NGF expression and secretion by adipocytes, using 3T3-L1 cells. Although interleukin (IL)-1 beta, IL-10, and IL-18 each induced a small decrease in NGF mRNA level in 3T3-L1 adipocytes, there was no significant effect of these cytokines on NGF secretion. A small reduction in NGF expression and/or secretion was also observed with adiponectin and prostaglandins PGE(2), PGF(2 alpha), and PGI(2). In marked contrast, prostaglandin PGD(2) induced a major, dose-dependent increase (up to 20- to 40-fold) in NGF expression and secretion. The PGD(2) metabolites, PGJ(2) and Delta(12)-PGJ(2), also induced major increases (up to 30-fold) in NGF production. A further metabolite of PGJ(2), 15-deoxy-Delta(12,14)-PGJ(2), a peroxisome proliferator-activated receptor-gamma agonist, led paradoxically to a small increase in NGF mRNA level but a fall in NGF secretion. Both PGD(2) and PGJ(2) induced significant increases in NGF gene expression by 4 h after their addition. It is concluded that PGD(2) and the J series prostaglandins, PGJ(2) and Delta(12)-PGJ(2), can play a significant role in the regulation of NGF production by white adipocytes. These results provide support for the view that NGF is an important inflammatory response protein, as well as a target-derived neurotrophin, in white adipose tissue.