Sanfilippo L, Li C K, Seth R, Balwin T J, Menozzi M G, Mahida Y R
Divisions of Gastroenterology and Pathology, and Institute of Infections and Immunity, University of Nottingham, UK.
Clin Exp Immunol. 2000 Mar;119(3):456-63. doi: 10.1046/j.1365-2249.2000.01155.x.
Bacteroides fragilis toxin (BFT) has been shown to be capable of inducing intestinal mucosal inflammation in animals. Such inflammation may be responsible for diarrhoea, which occurs in some, but not all human carriers of enterotoxigenic strains of B. fragilis (ETBF). We have studied responses to BFT by different human intestinal epithelial cell lines and subsequently investigated the expression of IL-8 and TGF-beta by T84 cells. The latter were selected because their responses to BFT, characterized by morphological changes and cell death by apoptosis, were similar to those we have recently observed in primary human colonocytes. We show that BFT dose-dependently increased the expression of transcripts and protein of the polymorphonuclear cell chemoattractant IL-8. BFT also dose-dependently induced the release of TGF-beta, which has been shown to enhance the repair of the injured intestinal epithelium. However, the secreted TGF-beta was almost exclusively in the biologically inactive form, as determined by Mv1Lu bioassay. Our studies therefore suggest that exposure of colonic epithelial cells in vivo to high concentrations of BFT can initiate an inflammatory response via secreted IL-8. BFT-induced release of latent TGF-beta may facilitate the subsequent repair of the injured epithelium, following its activation by proteases from neighbouring cells. Variation in cytokine responses by colonic epithelial cells in vivo could be an important determinant in the development of mucosal disease and symptoms in response to ETBF.
脆弱拟杆菌毒素（BFT）已被证明能够在动物体内诱导肠道黏膜炎症。这种炎症可能是导致腹泻的原因，腹泻发生在部分但并非所有携带产肠毒素脆弱拟杆菌（ETBF）的人类携带者中。我们研究了不同人类肠道上皮细胞系对BFT的反应，随后研究了T84细胞中白细胞介素-8（IL-8）和转化生长因子-β（TGF-β）的表达。选择T84细胞是因为它们对BFT的反应，其特征为形态变化和通过凋亡导致的细胞死亡，与我们最近在原代人结肠细胞中观察到的反应相似。我们发现，BFT以剂量依赖的方式增加了多形核细胞趋化因子IL-8的转录本和蛋白质表达。BFT还以剂量依赖的方式诱导了TGF-β的释放，TGF-β已被证明可促进受损肠道上皮的修复。然而，通过Mv1Lu生物测定法确定，分泌的TGF-β几乎完全处于生物学无活性形式。因此，我们的研究表明，体内结肠上皮细胞暴露于高浓度BFT可通过分泌的IL-8引发炎症反应。BFT诱导的潜伏TGF-β释放可能在其被邻近细胞的蛋白酶激活后促进受损上皮的后续修复。体内结肠上皮细胞细胞因子反应的差异可能是对ETBF产生黏膜疾病和症状的一个重要决定因素。
