Department of Medicine I (Gastroenterology), University of Ulm, Ulm, Germany.
Med Sci Monit. 2010 Jun;16(6):BR161-7.
The biologic effects of endothelin-1 (ET-1) are not limited to its vasoconstricting activity. A new and highly interesting role of the endothelin axis is its involvement in immune functions. As ET-1 is highly increased during gut inflammation, the aim of this study was to see if the endothelin axis influences enteric glia cell (EGC) functions, and through them, the immune response, during gut inflammation.
MATERIAL/METHODS: Cultured EGCs were treated with interleukin-1 beta (IL-1 beta), tumor necrosis factor-alpha (TNFalpha), IL-4, interferon-gamma, and ET-1. Secretion of ET-1 was detected by ELISA. Cultured EGCs were labeled with anti-glial fibrillary acidic protein (GFAP), endothelin-A (ETA), and endothelin-B (ETB), antibodies. The expression of ETA and ETB receptors was evaluated using reverse transcription PCR. Glial fibrillary acidic protein expression was determined by Western blot.
ET-1 secretion of EGCs could be stimulated by IL-1 beta and TNFalpha in a time and dose-dependent manner, whereas IL-4 and interferon-gamma showed no effect on ET-1 production. Cultured EGCs expressed ETA and ETB-receptors. Endothelin B mRNA expression was increased after incubation with IL-1 beta. Incubation of cells with IL-1 beta, TNFalpha, and ET-1 led to a significant increase of GFAP in EGCs.
Enteric glia cells express functional ETA and ETB receptors and produce huge amounts of ET-1 during gut inflammation, which increase GFAP expression in EGCs. These ET-1/ET receptors autocrine or paracrine loops might provide a new means to modulate EGC function, such as change in gut motility, cytokine production, and regulating gut homeostasis.
内皮素-1（ET-1）的生物学效应不仅限于其血管收缩活性。内皮素轴的一个新的、非常有趣的作用是其参与免疫功能。由于 ET-1 在肠道炎症期间高度增加，本研究的目的是观察内皮素轴是否影响肠胶质细胞（EGC）的功能，并通过它们影响肠道炎症期间的免疫反应。
材料/方法：用白细胞介素-1β（IL-1β）、肿瘤坏死因子-α（TNFα）、IL-4、干扰素-γ和 ET-1 处理培养的 EGC。通过 ELISA 检测 ET-1 的分泌。用抗胶质纤维酸性蛋白（GFAP）、内皮素-A（ETA）和内皮素-B（ETB）抗体标记培养的 EGC。使用逆转录 PCR 评估 ETA 和 ETB 受体的表达。通过 Western blot 测定 GFAP 表达。
EGC 的 ET-1 分泌可被 IL-1β和 TNFα以时间和剂量依赖的方式刺激，而 IL-4 和干扰素-γ对 ET-1 的产生没有影响。培养的 EGC 表达 ETA 和 ETB 受体。用 IL-1β孵育后，内皮素 B mRNA 表达增加。用 IL-1β、TNFα 和 ET-1 孵育细胞导致 EGC 中 GFAP 表达显著增加。
肠胶质细胞在肠道炎症期间表达功能性 ETA 和 ETB 受体，并产生大量的 ET-1，这增加了 EGC 中的 GFAP 表达。这些 ET-1/ET 受体自分泌或旁分泌环可能为调节 EGC 功能提供一种新的手段，例如改变肠道运动、细胞因子产生和调节肠道内稳态。
