Upregulation of Fas-Fas-L (CD95/CD95L)-mediated epithelial apoptosis--a putative role in pouchitis?

Hdl Handle:
http://hdl.handle.net/10147/209079
Title:
Upregulation of Fas-Fas-L (CD95/CD95L)-mediated epithelial apoptosis--a putative role in pouchitis?
Authors:
Coffey, J C; Bennett, M W; Wang, J H; O'Connell, J; Neary, P; Shanahan, F; Redmond, H P; Kirwan, W O
Affiliation:
Department of Academic Surgery, Cork University Hospital, Cork, Ireland.
Citation:
J Surg Res. 2001 Jun 1;98(1):27-32.
Journal:
The Journal of surgical research
Issue Date:
3-Feb-2012
URI:
http://hdl.handle.net/10147/209079
DOI:
10.1006/jsre.2001.6129
PubMed ID:
11368534
Abstract:
INTRODUCTION: Ileal pouch-anal anastomosis (IPAA) remains the gold standard for patients with refractory ulcerative colitis. Pouchitis causes considerable morbidity in 40% of patients with IPAA. This study examined the role of increased epithelial apoptosis in the etiology of pouchitis. METHODS: Following ethical approval pouch biopsies taken from patients with a history of pouchitis were compared with age-matched controls from patients who were pouchitis free. Apoptosis was detected immunohistochemically using a monoclonal antibody (M30) and terminal deoxyribonucleotidyl transferase (TDT)-mediated dUTP-digoxigenin end labeling (TUNEL). Villous atrophy was assessed histologically and correlated with levels of apoptosis. Epithelial Fas-ligand (L) was also assessed immunohistochemically. RESULTS: A significant increase in TUNEL staining was seen at the epithelial but not at the lamina propria level for known pouchitis patients versus controls (0.091 vs 0.035; P < 0.01). Similarly, epithelial M30 immunoreactivity (0.225 vs 0.082; P < 0.05) and villous atrophy (0.035 vs 0.10; P < 0.05) were significantly increased in pouches with previous pouchitis when compared with normal pouches. Upregulation of Fas-L expression was characteristic of this epithelium. Mononuclear cells were strongly positive for Fas-L. Increased epithelial levels of apoptosis correlated with increased levels of villous atrophy. CONCLUSIONS: Our data suggest a role for elevated Fas-Fas-L (CD95-CD95L)-mediated epithelial apoptosis in the etiology of pouchitis. Increased levels of villous atrophy may result from increased apoptosis and thereby predispose to infection by otherwise apathogenic organisms.
Language:
eng
MeSH:
Adolescent; Adult; Antibodies, Monoclonal; Antigens, CD95/*physiology; Apoptosis/*physiology; Atrophy; Child; Fas Ligand Protein; Humans; Ileum/pathology/*physiopathology; Immunohistochemistry; In Situ Nick-End Labeling; Intestinal Mucosa/pathology/*physiopathology; Membrane Glycoproteins/metabolism/*physiology; Microvilli/pathology; Middle Aged; Pouchitis/pathology/*physiopathology; Up-Regulation
ISSN:
0022-4804 (Print); 0022-4804 (Linking)

Full metadata record

DC FieldValue Language
dc.contributor.authorCoffey, J Cen_GB
dc.contributor.authorBennett, M Wen_GB
dc.contributor.authorWang, J Hen_GB
dc.contributor.authorO'Connell, Jen_GB
dc.contributor.authorNeary, Pen_GB
dc.contributor.authorShanahan, Fen_GB
dc.contributor.authorRedmond, H Pen_GB
dc.contributor.authorKirwan, W Oen_GB
dc.date.accessioned2012-02-03T15:11:42Z-
dc.date.available2012-02-03T15:11:42Z-
dc.date.issued2012-02-03T15:11:42Z-
dc.identifier.citationJ Surg Res. 2001 Jun 1;98(1):27-32.en_GB
dc.identifier.issn0022-4804 (Print)en_GB
dc.identifier.issn0022-4804 (Linking)en_GB
dc.identifier.pmid11368534en_GB
dc.identifier.doi10.1006/jsre.2001.6129en_GB
dc.identifier.urihttp://hdl.handle.net/10147/209079-
dc.description.abstractINTRODUCTION: Ileal pouch-anal anastomosis (IPAA) remains the gold standard for patients with refractory ulcerative colitis. Pouchitis causes considerable morbidity in 40% of patients with IPAA. This study examined the role of increased epithelial apoptosis in the etiology of pouchitis. METHODS: Following ethical approval pouch biopsies taken from patients with a history of pouchitis were compared with age-matched controls from patients who were pouchitis free. Apoptosis was detected immunohistochemically using a monoclonal antibody (M30) and terminal deoxyribonucleotidyl transferase (TDT)-mediated dUTP-digoxigenin end labeling (TUNEL). Villous atrophy was assessed histologically and correlated with levels of apoptosis. Epithelial Fas-ligand (L) was also assessed immunohistochemically. RESULTS: A significant increase in TUNEL staining was seen at the epithelial but not at the lamina propria level for known pouchitis patients versus controls (0.091 vs 0.035; P < 0.01). Similarly, epithelial M30 immunoreactivity (0.225 vs 0.082; P < 0.05) and villous atrophy (0.035 vs 0.10; P < 0.05) were significantly increased in pouches with previous pouchitis when compared with normal pouches. Upregulation of Fas-L expression was characteristic of this epithelium. Mononuclear cells were strongly positive for Fas-L. Increased epithelial levels of apoptosis correlated with increased levels of villous atrophy. CONCLUSIONS: Our data suggest a role for elevated Fas-Fas-L (CD95-CD95L)-mediated epithelial apoptosis in the etiology of pouchitis. Increased levels of villous atrophy may result from increased apoptosis and thereby predispose to infection by otherwise apathogenic organisms.en_GB
dc.language.isoengen_GB
dc.subject.meshAdolescenten_GB
dc.subject.meshAdulten_GB
dc.subject.meshAntibodies, Monoclonalen_GB
dc.subject.meshAntigens, CD95/*physiologyen_GB
dc.subject.meshApoptosis/*physiologyen_GB
dc.subject.meshAtrophyen_GB
dc.subject.meshChilden_GB
dc.subject.meshFas Ligand Proteinen_GB
dc.subject.meshHumansen_GB
dc.subject.meshIleum/pathology/*physiopathologyen_GB
dc.subject.meshImmunohistochemistryen_GB
dc.subject.meshIn Situ Nick-End Labelingen_GB
dc.subject.meshIntestinal Mucosa/pathology/*physiopathologyen_GB
dc.subject.meshMembrane Glycoproteins/metabolism/*physiologyen_GB
dc.subject.meshMicrovilli/pathologyen_GB
dc.subject.meshMiddle Ageden_GB
dc.subject.meshPouchitis/pathology/*physiopathologyen_GB
dc.subject.meshUp-Regulationen_GB
dc.titleUpregulation of Fas-Fas-L (CD95/CD95L)-mediated epithelial apoptosis--a putative role in pouchitis?en_GB
dc.contributor.departmentDepartment of Academic Surgery, Cork University Hospital, Cork, Ireland.en_GB
dc.identifier.journalThe Journal of surgical researchen_GB
dc.description.provinceMunster-

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