Induction of colitis causes inflammatory responses in fat depots: Evidence for substance P pathways in human mesenteric preadipocytes
Induction of colitis causes inflammatory responses in fat depots: Evidence for substance P pathways in human mesenteric preadipocytes
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DOI：
10.1073/pnas.0600821103
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发表时间：
2006-03-28
影响因子：
11.1
通讯作者：
Pothoulakis, C
中科院分区：
文献类型：
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作者：
Karagiannides, L;Kokkotou, E;Pothoulakis, C
小鼠结肠内给药三硝基苯磺酸会引起结肠炎症，并伴有促炎细胞因子和肠系膜近端脂肪库中P物质（SP）、神经激肽1受体（NK-1R）的表达增加。我们还研究了人类肠系膜前脂肪细胞是否含有NK-1R，并检查了这些细胞暴露于SP的功能后果，因为它与促炎信号传导有关。我们发现人肠系膜前脂肪细胞在mRNA和蛋白水平上表达NK-1R。人肠系膜前脂肪细胞暴露于SP后，使NK-1R mRNA和蛋白表达增加3倍，并刺激IL-8 mRNA表达和蛋白分泌。当用特异性NK-1R拮抗剂CJ 012255预处理这些细胞时，这种作用被消除。此外，人肠系膜前脂肪细胞转染含有NF-kappa B位点突变的IL-8启动子的荧光素酶启动子/报告系统后，失去了对SP的应答能力，这表明SP诱导的IL-8表达依赖于NF-kappa B。本报告表明，人肠系膜前脂肪细胞含有与促炎通路相关的功能性SIP受体，而SP可以直接增加NK-1R的表达。我们推测，肠系膜脂肪库可能通过sp - nk - 1r相关途径参与肠道炎症反应，以及对结肠持续炎症存在的其他全身反应。
Intracolonic administration of trinitrobenzene sulfonic acid in mice causes inflammation in the colon that is accompanied by increased expression of proinflammatory cytokines and of the substance P (SP), neurokinin 1 receptor (NK-1R) in the proximal mesenteric fat depot. We also investigated whether human mesenteric preadipocytes contain NK-1R and examined the functional consequences of exposure of these cells to SP as it relates to proinflammatory signaling. We found that human mesenteric preadipocytes express NK-1R both at the mRNA and protein levels. Exposure of human mesenteric preadipocytes to SP increased NK-1R mRNA and protein expression by 3-fold, and stimulated IL-8 mRNA expression and protein secretion. This effect was abolished when these cells were pretreated with the specific NK-1R antagonist CJ 012,255. Moreover, human mesenteric preadipocytes transfected with a luciferase promoter/reporter system containing the IL-8 promoter with a mutated NF-kappa B site lost their ability to respond to SP, indicating that SP-induced IL-8 expression is NF-kappa B-dependent. This report indicates that human mesenteric preadipocytes contain functional SIP receptors that are linked to proinflammatory pathways, and that SP can directly increase NK-1R expression. We speculate that mesenteric fat depots may participate in intestinal inflammatory responses via SP-NK-1R-related pathways, as well as other systemic responses to the presence of an ongoing inflammation of the colon.