Keates S, Keates A C, Mizoguchi E, Bhan A, Kelly C P
Gastroenterology Division, Beth Israel Deaconess Medical Center, Boston, Massachusetts 02215, USA.
Am J Physiol. 1997 Jul;273(1 Pt 1):G75-82. doi: 10.1152/ajpgi.1997.273.1.G75.
Epithelial cell-derived neutrophil-activating protein-78 (ENA-78) is a neutrophil-directed C-X-C chemokine. We report that Caco-2 and T84 human intestinal epithelial cells produce ENA-78 after stimulation by interleukin (IL)-1 beta or tumor necrosis factor-alpha. Caco-2 cells show increased IL-8 production at 4-12 h and increased ENA-78 production at 8-24 h after cytokine stimulation. Immunohistochemical studies in normal human colon and in ulcerative colitis demonstrate ENA-78 immunoreactivity principally associated with crypt epithelial cells. Furthermore, human colonic tissues from patients with ulcerative colitis show elevated levels of ENA-78 mRNA (24-fold increase, P < 0.01) and protein (4-fold increase, P < 0.05) compared with normal controls. Thus ENA-78 is produced in normal colon and in ulcerative colitis and is predominantly of enterocyte origin. The kinetics of ENA-78 induction in human colon epithelial cell lines are delayed and prolonged compared with IL-8. We propose that ENA-78 and IL-8 serve complementary and sequential roles in neutrophil recruitment in ulcerative colitis. ENA-78 as an enterocyte-derived, neutrophil-activating chemokine may be especially important in neutrophil recruitment from the lamina propria into the epithelial layer.
上皮细胞源性中性粒细胞激活蛋白78（ENA - 78）是一种趋化中性粒细胞的C - X - C趋化因子。我们报告称，白细胞介素（IL）-1β或肿瘤坏死因子-α刺激后，人结肠腺癌细胞（Caco - 2）和人小肠上皮细胞（T84）可产生ENA - 78。细胞因子刺激后，Caco - 2细胞在4 - 12小时白细胞介素-8（IL - 8）产生增加，在8 - 24小时ENA - 78产生增加。在正常人结肠和溃疡性结肠炎中的免疫组织化学研究表明，ENA - 78免疫反应性主要与隐窝上皮细胞相关。此外，与正常对照相比，溃疡性结肠炎患者的人结肠组织中ENA - 78信使核糖核酸（mRNA）水平升高（增加24倍，P < 0.01），蛋白质水平升高（增加4倍，P < 0.05）。因此，ENA - 78在正常结肠和溃疡性结肠炎中均有产生，且主要来源于肠上皮细胞。与IL - 8相比，人结肠上皮细胞系中ENA - 78诱导的动力学过程延迟且延长。我们认为，ENA - 78和IL - 8在溃疡性结肠炎中性粒细胞募集中发挥互补和相继的作用。ENA - 78作为一种由肠上皮细胞衍生的、激活中性粒细胞的趋化因子，在中性粒细胞从固有层募集到上皮层的过程中可能尤为重要。
