Somatostatin through its specific receptor inhibits spontaneous and TNF-α- and bacteria-induced IL-8 and IL-1β secretion from intestinal epithelial cells
Somatostatin through its specific receptor inhibits spontaneous and TNF-α- and bacteria-induced IL-8 and IL-1β secretion from intestinal epithelial cells
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DOI：
10.4049/jimmunol.165.6.2955
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发表时间：
2000-09-15
影响因子：
4.4
通讯作者：
Levite, M
中科院分区：
文献类型：
--
作者：
Chowers, Y;Cahalon, L;Levite, M
肠上皮细胞分泌促炎细胞因子和趋化因子，这在粘膜防御中是至关重要的。然而，这种分泌必须受到严格的调控，因为不受控制的促炎介质的分泌可能会导致慢性炎症和粘膜损伤，本研究的目的是确定肠粘液中分泌的生长抑素是否调节肠道上皮细胞分泌细胞因子。用生长抑素或其合成类似物奥曲肽处理肠上皮细胞系Caco-2和HT-29后，测定其自发分泌IL-8和IL-1β的能力，以及由肿瘤坏死因子α和沙门氏菌诱导的分泌IL-8和IL-1β的能力。在生理纳摩尔浓度下，生长抑素显著抑制自发的和由肿瘤坏死因子α诱导的IL-8和IL-1β的分泌，这种抑制作用呈剂量依赖关系，在3 nM时阻断达90%；此外，生长抑素完全抑制沙门氏菌入侵后IL-8和IL-1β的分泌增加，主要刺激生长抑素受体2和5亚型的奥曲肽对IL-8和IL-1β的分泌也有类似的影响，生长抑素拮抗剂环状生长抑素完全阻断生长抑素和奥曲肽诱导的抑制作用。这种抑制作用与IL-8和IL-1β的mRNA浓度降低有关，对细胞活力无影响。这些结果表明，生长抑素通过直接与其在肠上皮细胞上表达的特异性受体相互作用，通过转录调节机制下调促炎介质的分泌。这些结果表明，生长抑素在细菌入侵等生理和病理生理刺激后，对肠上皮细胞的粘膜炎症反应具有积极的调节作用。
Intestinal epithelial cells secrete proinflammatory cytokines and chemokines that are crucial in mucosal defense. However, this secretion must be tightly regulated, because uncontrolled secretion of proinflammatory mediators may lead to chronic inflammation and mucosal damage, The aim of this study was to determine whether somatostatin, secreted within the intestinal mucose, regulates secretion of cytokines from intestinal epithelial cells. The spontaneous as well as TNF-alpha- and Salmonella-induced secretion of IL-8 and IL-1 beta derived from intestinal cell lines Caco-2 and HT-29 was measured after treatment with somatostatin or its synthetic analogue, octreotide. Somatostatin, at physiological nanomolar concentrations, markedly inhibited the spontaneous and TNF-alpha -induced secretion of IL-8 and IL-1 beta, This inhibition was dose dependent, reaching >90% blockage at 3 nM, Furthermore, somatostatin completely abrogated the increased secretion of IL-8 and IL-1 beta after invasion by Salmonella, Octreotide, which mainly stimulates somatostatin receptor subtypes 2 and 5, affected the secretion of IL-8 and IL-1 beta similarly, and the somatostatin antagonist cyclo-somatostatin completely blocked the somatostatin- and octreotide-induced inhibitory effects. This inhibition was correlated to a reduction of the mRNA concentrations of IL-8 and IL-1 beta, No effect was noted regarding cell viability, These results indicate that somatostatin, by directly interacting with its specific receptors that are expressed on intestinal epithelial cells, down-regulates proinflammatory mediator secretion by a mechanism involving the regulation of transcription, These findings suggest that somatostatin plays an active role in regulating the mucosal inflammatory response of intestinal epithelial cells after physiological and pathophysiological stimulations such as bacterial invasion.