Intestinal intraepithelial lymphocyte derived angiotensin converting enzyme modulates epithelial cell apoptosis.
Details
Serval ID
serval:BIB_8F31D85C4100
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Intestinal intraepithelial lymphocyte derived angiotensin converting enzyme modulates epithelial cell apoptosis.
Journal
Apoptosis
ISSN
1360-8185 (Print)
ISSN-L
1360-8185
Publication state
Published
Issued date
2005
Peer-reviewed
Oui
Volume
10
Number
6
Pages
1305-1315
Language
english
Notes
Publication types: Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't Publication Status: ppublish
Abstract
BACKGROUND & AIMS: Intestinal adaptation in short bowel syndrome (SBS) consists of increased epithelial cell (EC) proliferation as well as apoptosis. Previous microarray analyses of intraepithelial lymphocytes (IEL) gene expression after SBS showed an increased expression of angiotensin converting enzyme (ACE). Because ACE has been shown to promote alveolar EC apoptosis, we examined if IEL-derived ACE plays a role in intestinal EC apoptosis.
METHODS: Mice underwent either a 70% mid-intestinal resection (SBS group) or a transection (Sham group) and were studied at 7 days. ACE expression was measured, and ACE inhibition (ACE-I, enalaprilat) was used to assess ACE function.
RESULTS: IEL-derived ACE was significantly elevated in SBS mice. The addition of an ACE-I to SBS mice resulted in a significant decline in EC apoptosis. To address a possible mechanism, tumor necrosis factor alpha (TNF-alpha) mRNA expression was measured. TNF-alpha was significantly increased in SBS mice, and decreased with ACE-I. Interestingly, ACE-I was not able to decrease EC apoptosis in TNF-alpha knockout mice.
CONCLUSIONS: This study shows a previously undescribed expression of ACE by IEL. SBS was associated with an increase in IEL-derived ACE. ACE appears to be associated with an up-regulation of intestinal EC apoptosis. ACE-I significantly decreased EC apoptosis.
METHODS: Mice underwent either a 70% mid-intestinal resection (SBS group) or a transection (Sham group) and were studied at 7 days. ACE expression was measured, and ACE inhibition (ACE-I, enalaprilat) was used to assess ACE function.
RESULTS: IEL-derived ACE was significantly elevated in SBS mice. The addition of an ACE-I to SBS mice resulted in a significant decline in EC apoptosis. To address a possible mechanism, tumor necrosis factor alpha (TNF-alpha) mRNA expression was measured. TNF-alpha was significantly increased in SBS mice, and decreased with ACE-I. Interestingly, ACE-I was not able to decrease EC apoptosis in TNF-alpha knockout mice.
CONCLUSIONS: This study shows a previously undescribed expression of ACE by IEL. SBS was associated with an increase in IEL-derived ACE. ACE appears to be associated with an up-regulation of intestinal EC apoptosis. ACE-I significantly decreased EC apoptosis.
Keywords
Angiotensin-Converting Enzyme Inhibitors/administration & dosage, Angiotensin-Converting Enzyme Inhibitors/pharmacology, Animals, Antigens, CD95/genetics, Antigens, CD95/metabolism, Apoptosis/drug effects, Body Weight, Cell Proliferation/drug effects, Cytokines/genetics, Cytokines/metabolism, Epithelial Cells/cytology, Epithelial Cells/drug effects, Fas Ligand Protein/genetics, Fas Ligand Protein/metabolism, Gene Expression Regulation/drug effects, Inflammation Mediators/metabolism, Intestinal Mucosa/drug effects, Intestinal Mucosa/enzymology, Intestines/cytology, Intestines/drug effects, Lymphocytes/cytology, Lymphocytes/drug effects, Male, Mice, Mice, Inbred C57BL, Peptidyl-Dipeptidase A/genetics, Peptidyl-Dipeptidase A/metabolism, RNA, Messenger/genetics, RNA, Messenger/metabolism, Short Bowel Syndrome/enzymology, Short Bowel Syndrome/pathology, Tumor Necrosis Factor-alpha/metabolism
Pubmed
Web of science
Create date
21/02/2015 14:10
Last modification date
20/08/2019 15:52
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