title: Differential levels of granzyme B, regulatory cytokines, and apoptosis in Crohn's disease and ulcerative colitis at first presentation.
abstract: The mechanisms of tissue damage in ulcerative colitis and Crohn's disease may reflect disordered humoral or cell-mediated effector mechanisms, respectively. Mucosal biopsies from untreated inflammatory bowel disease patients and normal controls were analysed for the expression of granzyme B, a cytotoxic effector molecule specifically associated with cell-mediated immunity, and for regulatory cytokines. Messenger RNA (mRNA) was analysed by reverse transcription-polymerase chain reaction and enzyme-linked oligonucleotide chemiluminescence assay. Mucosal biopsies were analysed by immunohistochemistry for granzyme B protein and lymphocyte markers and for the presence of apoptotic cells by terminal deoxynucleotidyl transferase end labelling. Granzyme B mRNA was elevated in Crohn's disease, but not in ulcerative colitis or control mucosal biopsies. Granzyme B mRNA levels correlated with interferon gamma mRNA levels in Crohn's disease. Granzyme B was expressed in CD3+, CD8+ T cells in the lamina propria of Crohn's disease mucosa and there were significantly more apoptotic cells in the lamina propria in Crohn's disease. In conclusion, granzyme B-expressing T lymphocytes are present in the focal mucosal lesions of Crohn's disease, together with spatially related apoptotic cell death. These results support the hypothesis that T-cell-mediated cytotoxic effector mechanisms may play a role in Crohn's disease.
authors.affiliation: Department of Clinical Laboratory Sciences, University Hospital, Nottingham, UK.
authors.forename: D
authors.initials: D
authors.lastname: Jenkins
authors.forename: R
authors.initials: R
authors.lastname: Seth
authors.forename: J A
authors.initials: JA
authors.lastname: Kummer
authors.forename: B B
authors.initials: BB
authors.lastname: Scott
authors.forename: C J
authors.initials: CJ
authors.lastname: Hawkey
authors.forename: R A
authors.initials: RA
authors.lastname: Robins
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D017209:Apoptosis; D002648:Child; D003093:Colitis, Ulcerative / Q000201:enzymology / Q000276:immunology* / Q000473:pathology; D003424:Crohn Disease / Q000201:enzymology / Q000276:immunology* / Q000473:pathology; D016207:Cytokines / Q000235:genetics / Q000378:metabolism*; D005260:Female; D015870:Gene Expression; D053804:Granzymes; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000235:genetics; D012697:Serine Endopeptidases / Q000235:genetics / Q000378:metabolism*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology
chemical_list: D016207:Cytokines; D012333:RNA, Messenger; C509213:GZMB protein, human; D053804:Granzymes; D012697:Serine Endopeptidases