Riegler M, Sedivy R, Sogukoglu T, Castagliuolo I, Pothoulakis C, Cosentini E, Bischof G, Hamilton G, Teleky B, Feil W, Lamont J T, Wenzl E
University Clinic of Surgery, University of Vienna, Austria.
Am J Physiol. 1997 Nov;273(5):G1014-22. doi: 10.1152/ajpgi.1997.273.5.G1014.
Epidermal growth factor (EGF) exhibits a cytoprotective effect on gastrointestinal epithelia via a receptor-mediated mechanism. We investigated the effect of EGF on Clostridium difficile toxin A (TxA)- and toxin B (TxB)-induced damage of human colon. Ussing-chambered colonic mucosa was exposed serosally to EGF before and during luminal exposure to TxA and TxB. Resistance was calculated from potential difference and short-circuit current. Epithelial damage was assessed by light microscopy and alteration of F-actin by fluoresceinated phalloidin. Luminal exposure of colonic strips to TxA and TxB caused a time- and dose-dependent decrease in electrical resistance, necrosis and dehiscence of colonocytes, and disruption and condensation of enterocyte F-actin. These effects were inhibited by prior, but not simultaneous, serosal application of EGF (20 nM). Administration of the tyrosine kinase inhibitor genistein (10(-6) M) inhibited the protective effects of EGF. We conclude that EGF protects against TxA and TxB probably by stabilizing the cytoskeleton, the main target of these toxins.
表皮生长因子（EGF）通过受体介导机制对胃肠道上皮细胞发挥细胞保护作用。我们研究了EGF对艰难梭菌毒素A（TxA）和毒素B（TxB）诱导的人结肠损伤的影响。在管腔暴露于TxA和TxB之前及期间，将尤斯灌流室的结肠黏膜浆膜面暴露于EGF。根据电位差和短路电流计算电阻。通过光学显微镜评估上皮损伤，并使用荧光鬼笔环肽评估F-肌动蛋白的改变。结肠条带管腔暴露于TxA和TxB会导致电阻呈时间和剂量依赖性降低、结肠细胞坏死和裂开，以及肠上皮细胞F-肌动蛋白的破坏和凝聚。预先（而非同时）在浆膜面应用EGF（20 nM）可抑制这些效应。给予酪氨酸激酶抑制剂染料木黄酮（10⁻⁶ M）可抑制EGF的保护作用。我们得出结论，EGF可能通过稳定细胞骨架来保护免受TxA和TxB的损伤，而细胞骨架是这些毒素的主要作用靶点。
