Netsch M I, Gutmann H, Aydogan C, Drewe J
Department of Research and Clinical Pharmacology, University Hospital, Basel, Switzerland.
Planta Med. 2006 Jun;72(8):697-702. doi: 10.1055/s-2006-931597. Epub 2006 May 31.
The chemokine interleukin (IL)-8 is a cytokine involved in neutrophil attraction and activation and elevated levels have been observed in intestinal inflammation. Anti-inflammatory activities have been attributed to green tea or its major constituent (-)-epigallocatechin gallate (EGCG). In this study, we investigated the effects of a defined green tea extract (GTE) or EGCG on basal or IL-1beta-induced IL-8 expression and secretion in the human gastrointestinal epithelial cell line Caco-2. mRNA expression levels were determined by quantitative RT-PCR. GTE significantly induced IL-8 mRNA expression, which was not mediated indirectly via an induction of IL-1beta mRNA expression. EGCG only exerted a weak although significant induction of IL-8 mRNA expression at the highest concentration. Intracellular and extracellular protein levels were analyzed by an enzyme-linked immunosorbent assay. GTE and EGCG significantly decreased secreted IL-8 concentrations. Determination of intracellular and secreted IL-8 concentrations after 24 h, 48 h, and 72 h of incubation suggested that GTE specifically inhibited IL-8 secretion while inducing DE NOVO synthesis of IL-8. The IL-1beta-mediated increase of IL-8 secretion was significantly inhibited by GTE in a dose-dependent manner. At the highest concentration, GTE inhibited IL-1beta-induced IL-8 secretion to a similar extent as found for brefeldin A, an inhibitor of vesicular transport. These results suggest that GTE may exert an anti-inflammatory activity in enterocytes, which may be useful for the treatment of intestinal inflammation.
趋化因子白细胞介素(IL)-8是一种参与中性粒细胞吸引和激活的细胞因子,在肠道炎症中可观察到其水平升高。绿茶或其主要成分(-)-表没食子儿茶素没食子酸酯(EGCG)具有抗炎活性。在本研究中,我们调查了特定绿茶提取物(GTE)或EGCG对人胃肠道上皮细胞系Caco-2中基础或IL-1β诱导的IL-8表达和分泌的影响。通过定量RT-PCR测定mRNA表达水平。GTE显著诱导IL-8 mRNA表达,这并非通过诱导IL-1β mRNA表达间接介导。EGCG在最高浓度时仅对IL-8 mRNA表达产生微弱但显著的诱导作用。通过酶联免疫吸附测定分析细胞内和细胞外蛋白水平。GTE和EGCG显著降低分泌的IL-8浓度。孵育24小时、48小时和72小时后测定细胞内和分泌的IL-8浓度表明,GTE特异性抑制IL-8分泌,同时诱导IL-8的从头合成。GTE以剂量依赖方式显著抑制IL-1β介导的IL-8分泌增加。在最高浓度时,GTE抑制IL-1β诱导的IL-8分泌的程度与囊泡运输抑制剂布雷菲德菌素A相似。这些结果表明,GTE可能在肠细胞中发挥抗炎活性,这可能对肠道炎症的治疗有用。