Functional and biochemical characterization of epithelial bactericidal/permeability-increasing protein.

Details

Serval ID
serval:BIB_195096C91A93
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Functional and biochemical characterization of epithelial bactericidal/permeability-increasing protein.
Journal
American Journal of Physiology. Gastrointestinal and Liver Physiology
Author(s)
Canny G., Cario E., Lennartsson A., Gullberg U., Brennan C., Levy O., Colgan S.P.
ISSN
0193-1857
Publication state
Published
Issued date
03/2006
Peer-reviewed
Oui
Volume
290
Number
3
Pages
G557-567
Language
english
Notes
Publication types: Journal Article
Abstract
Epithelial cells of many mucosal organs have adapted to coexist with microbes and microbial products. In general, most studies suggest that epithelial cells benefit from interactions with commensal microorganisms present at the lumenal surface. However, potentially injurious molecules found in this microenvironment also have the capacity to elicit local inflammatory responses and even systemic disease. We have recently demonstrated that epithelia cells express the anti-infective molecule bactericidal/permeability-increasing protein (BPI). Here, we extend these findings to examine molecular mechanisms of intestinal epithelial cell (IEC) BPI expression and function. Initial experiments revealed a variance of BPI mRNA and protein expression among various IEC lines. Studies of BPI promoter expression in IECs identified regulatory regions of the BPI promoter and revealed a prominent role for CCAAT/enhancer binding protein and especially Sp1/Sp3 in the basal regulation of BPI. To assess the functional significance of this protein, we generated an IEC line stably transfected with full-length BPI. We demonstrated that, whereas epithelia express markedly less BPI protein than neutrophils, epithelial BPI contributes significantly to bacterial killing and attenuating bacterial-elicted proinflammatory signals. Additional studies in murine tissue ex vivo revealed that BPI is diffusely expressed along the crypt-villous axis and that epithelial BPI levels decrease along the length of the intestine. Taken together, these data confirm the transcriptional regulation of BPI in intestinal epithelia and provide insight into the relevance of BPI as an anti-infective molecule at intestinal surfaces.
Keywords
Animals, Antimicrobial Cationic Peptides, Blood Bactericidal Activity, Blood Proteins/genetics, Blood Proteins/physiology, CCAAT-Enhancer-Binding Proteins/physiology, Caco-2 Cells, Humans, Intestinal Mucosa/metabolism, Lipopolysaccharides/pharmacology, Membrane Proteins/genetics, Membrane Proteins/physiology, Mice, Promoter Regions, Genetic/physiology, Sp Transcription Factors/physiology
Pubmed
Web of science
Create date
18/01/2008 12:11
Last modification date
20/08/2019 12:50
Usage data