ENTEROCYTES ARE THE PRIMARY SOURCE OF THE CHEMOKINE ENA-78 IN NORMAL COLON AND ULCERATIVE-COLITIS

Epithelial cell-derived neutrophil-activating protein-78 (ENA-78) is a neutrophil-directed C-X-C chemokine. We report that Caco-2 and T84 hu man intestinal epithelial cells produce ENA-78 after stimulation by in terleukin (IL)-1 beta or tumor necrosis factor-alpha. Caco-2 cells sho w increased IL-8 production at 4-12 h and increased ENA-78 production at 8-24 h after cytokine stimulation. Immunohistochemical studies in n ormal human colon and in ulcerative colitis demonstrate ENA-78 immunor eactivity principally associated with crypt epithelial cells. Furtherm ore, human colonic tissues from patients with ulcerative colitis show elevated levels of ENA-78 mRNA (24-fold increase, P < 0.01) and protei n (4-fold increase, P < 0.05) compared with normal controls. Thus ENA- 78 is produced in normal colon and in ulcerative colitis and is predom inantly of enterocyte origin. The kinetics of ENA-78 induction in huma n colon epithelial cell lines are delayed and prolonged compared with IL-8. We propose that ENA-78 and IL-8 serve complementary and sequenti al 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.