TY - JOUR
T1 - Epithelial apoptosis: cause or consequence of ulcerative colitis?
AU - Seidelin, Jakob Benedict
AU - Nielsen, Ole Haagen
N1 - Keywords: Adolescent; Adult; Aged; Aged, 80 and over; Apoptosis; Biopsy; Case-Control Studies; Colitis, Ulcerative; Colon, Sigmoid; Colonoscopy; Epithelial Cells; Fas Ligand Protein; Female; Flow Cytometry; Glucocorticoids; Humans; Intestinal Mucosa; Male; Middle Aged; Prednisolone; Rectum; Treatment Outcome
PY - 2009
Y1 - 2009
N2 - OBJECTIVE: Epithelial apoptosis rates are increased in ulcerative colitis (UC). The increased apoptosis rate could expose mucosal cells to luminal pathogens and thereby be regarded as a primary pathogenic factor in UC. On the other hand, the local inflammatory reaction could cause epithelial apoptosis secondary to the release of cytotoxic mediators. If apoptosis is a primary defect, apoptosis rates could influence the degree of spreading of inflammation and the clinical course of UC. If apoptosis is a side effect of local inflammation, apoptosis rates would be expected only to correlate with the degree of local inflammation. The aim of the study was to investigate the relationship between epithelial apoptosis and clinical characteristics of UC. MATERIAL AND METHODS: Twenty patients with UC (12 with active disease) and 20 control subjects were included. Freshly isolated colonic epithelial cells were cultured. Apoptosis was determined by flow cytometry. Cells were stimulated with Fas ligand. The disease was characterized by endoscopic findings, microscopic inflammation grade, surrogate markers of disease activity (hemoglobin level, white blood cell count, C-reactive protein, or albumin), and the clinical course 6 months after biopsy. RESULTS: Epithelial apoptosis correlated with local inflammation, both macroscopic (p< 0.02) and microscopic (p< 0.008). Disease extent, disease course, or surrogate markers of disease activity did not correlate with apoptosis rate. However, increased microscopic inflammation inversely correlated with apoptosis response to the Fas ligand (p< 0.06). CONCLUSIONS: The epithelial apoptosis rate is influenced primarily by the local inflammatory response. Colonocytes upregulate cytoprotective mediators that decrease apoptosis susceptibility during active UC.
AB - OBJECTIVE: Epithelial apoptosis rates are increased in ulcerative colitis (UC). The increased apoptosis rate could expose mucosal cells to luminal pathogens and thereby be regarded as a primary pathogenic factor in UC. On the other hand, the local inflammatory reaction could cause epithelial apoptosis secondary to the release of cytotoxic mediators. If apoptosis is a primary defect, apoptosis rates could influence the degree of spreading of inflammation and the clinical course of UC. If apoptosis is a side effect of local inflammation, apoptosis rates would be expected only to correlate with the degree of local inflammation. The aim of the study was to investigate the relationship between epithelial apoptosis and clinical characteristics of UC. MATERIAL AND METHODS: Twenty patients with UC (12 with active disease) and 20 control subjects were included. Freshly isolated colonic epithelial cells were cultured. Apoptosis was determined by flow cytometry. Cells were stimulated with Fas ligand. The disease was characterized by endoscopic findings, microscopic inflammation grade, surrogate markers of disease activity (hemoglobin level, white blood cell count, C-reactive protein, or albumin), and the clinical course 6 months after biopsy. RESULTS: Epithelial apoptosis correlated with local inflammation, both macroscopic (p< 0.02) and microscopic (p< 0.008). Disease extent, disease course, or surrogate markers of disease activity did not correlate with apoptosis rate. However, increased microscopic inflammation inversely correlated with apoptosis response to the Fas ligand (p< 0.06). CONCLUSIONS: The epithelial apoptosis rate is influenced primarily by the local inflammatory response. Colonocytes upregulate cytoprotective mediators that decrease apoptosis susceptibility during active UC.
U2 - 10.3109/00365520903301212
DO - 10.3109/00365520903301212
M3 - Journal article
C2 - 19958058
SN - 0036-5521
VL - 44
SP - 1429
EP - 1434
JO - Scandinavian Journal of Gastroenterology
JF - Scandinavian Journal of Gastroenterology
IS - 12
ER -