Fas (CD95/APO-1)-Mediated Cell Apoptosis Plays A Role In Ulcerative Colitis

Objectives: To investigate the role of apoptosis induced by Fas/FasL in colonic epithelial cells and lamina propria mononuclear cells (LPMCs) on the pathogenesis of ulcerative colitis (UC).Materials and Methods: The patients with active UC or sporadic colonic polyps diagnosed by Department of Gastroenterology in Huaxi Hospital from May 2003 to February 2004 were recruited into the study trials. Diagnosis was established by clinical and pathologic criteria. The disease activity index of UC was graded according to Powell-Tuck grade system. The colonic biopsy specimens were collected from involved areas in patients with active UC and from normal areas in patients with sporadic colonic polyps. Biopsy specimens were processed for routine histological examination and for immunohistochemical evaluation of Fas, FasL, Ki-67 and active Caspase3 expression. For the detection of apoptosis in situ, terminal deoxynucleotidyl transferase-mediated nick end labeling staining (TUNEL) was used. Results:1. The analysis of experimental items between UC (n=54) and controls (n=11) 1.1 The apoptotic index (AT) of epithelial cells in UC was higher than that of controls, which was 5.98%(1.83%~19.46%) and 0.62%(0.00~2.03%) respectively. The expression indexes of proapoptotic proteins Fas and active Caspase3 in epithelial cells were dramatically increased compared with those of the controls (P<0.05), and so did the proliferation index (PI) of epithelial cells in UC (P<0.05). The AI/PI ratioof epithelial cells in UC was higher than that of controls. No FasL was found in ' epithelial cells from both UC and controls.1.2 The AI of LPMCs in UC was lower than that of controls, which was 8.11 %(0.31 %~54.17%) and 11.03%(7.53%~21.21%) respectively, and so did the expression index of active Caspase3 of LPMCs in UC. The expression indexes of Fas, Ki-67 and FasL of LPMCs in UC was higher than those of controls. It suggested that LPMCs in UC were less sensitive to apoptotic signal mediated by Fas.2. The analysis of correlation between experimental items in UC (n=54)There were significant positive correlations between P-T scores and AI, the expression indexes of Fas and active Caspase3 in epithelial cells. A significant positive correlation between P-T scores and the percentage of FasL was observed in LPMCs.3. The analysis of experimental items in UC followed up (n=l 7)3.1 The AI of epithelial cells was decreased in UC after regular treatment (PO.05), andO so did the expression of active Caspase3 (P<0.05). This suggested that the AI ofepithelial cells may contribute to the pathogenesis of UC, and active Caspase3 may play a role in apoptosis of epithelial cells.3.2 The AI of LPMCs was increased in UC after treatment, and the expression index of active Caspase3 LPMCs also increased. No significant difference in the expression index of Fas was found before and after treatment. Those suggested that LPMCs of active UC was not sensitive to the apoptosis mediated by Fas.Conclusions: Increased apoptosis of epithelial cells, decreased apoptosis and overproliferation of LPMCs might be the mechanism of UC pathogenesis. The abnormal regulation of apoptosis by Fas/FasL interaction may play an important role in those cells.