Branka J E, Vallette G, Jarry A, Bou-Hanna C, Lemarre P, Van P N, Laboisse C L
Groupe de Recherche Fonctions Secretoires des Epitheliums Digestifs, CJF INSERM 94-04, Faculte de Medecine, Nantes, France.
Gastroenterology. 1997 Jun;112(6):1887-94. doi: 10.1053/gast.1997.v112.pm9178681.
BACKGROUND & AIMS: Previous in vitro studies have shown that Clostridium difficile toxin A is able to directly affect the intestinal epithelial barrier function. The aim of this study was to examine the early effects of toxin A on mucin exocytosis and determine whether this toxin can induce the production of the chemokine interleukin 8 (IL-8) from human colonic epithelial cells.
Two model systems were used: the HT29-CI.16E colonic goblet cell line and primary cultures of human normal colonocytes.
Toxin A exerted a rapid and dose-related inhibition of stimulated mucin exocytosis without altering baseline (constitutive) mucin exocytosis from HT29-CI.16E cells. Toxin A was also able to induce the secretion of IL-8 from both HT29-CI.16E cells and primary cultures of human normal colonocytes, as early as 2-3 hours of incubation.
The results show that while toxin A is able to down-regulate stimulated mucin exocytosis, it is able to up-regulate the secretion of an important chemoattractant chemokine, IL-8. These modifications illustrate the ability of colonocytes to recruit inflammatory and immune cells that will eventually bring about major mucosal damage.
先前的体外研究表明，艰难梭菌毒素A能够直接影响肠道上皮屏障功能。本研究的目的是检测毒素A对粘蛋白胞吐作用的早期影响，并确定该毒素是否能诱导人结肠上皮细胞产生趋化因子白细胞介素8（IL-8）。
使用了两种模型系统：HT29-CI.16E结肠杯状细胞系和人正常结肠细胞原代培养物。
毒素A对刺激的粘蛋白胞吐作用产生快速且与剂量相关的抑制，而不改变HT29-CI.16E细胞的基线（组成性）粘蛋白胞吐作用。毒素A还能够早在孵育2-3小时后就诱导HT29-CI.16E细胞和人正常结肠细胞原代培养物分泌IL-8。
结果表明，虽然毒素A能够下调刺激的粘蛋白胞吐作用，但它能够上调一种重要的趋化性趋化因子IL-8的分泌。这些改变说明了结肠细胞招募炎症和免疫细胞的能力，而这些细胞最终会导致严重的粘膜损伤。
