Document Detail

Human pancreatic secretory trypsin inhibitor stabilizes intestinal mucosa against noxious agents.
MedLine Citation:
PMID:  17982125     Owner:  NLM     Status:  MEDLINE    
Pancreatic secretory trypsin inhibitor (PSTI) is a serine protease inhibitor, expressed in gut mucosa, whose function is unclear. We, therefore, examined the effects of PSTI on gut stability and repair. Transgenic mice overexpressing human PSTI within the jejunum (FABPi(-1178 to +28) hPSTI construct) showed no change in baseline morphology or morphometry but reduced indomethacin-induced injury in overexpressing hPSTI region by 42% (P < 0.01). Systemic recombinant hPSTI did not affect baseline morphology or morphometry but truncated injurious effects in prevention and recovery rat models of dextran-sodium-sulfate-induced colitis. In vitro studies showed PSTI stimulated cell migration but not proliferation of human colonic carcinoma HT29 or immortalized mouse colonic YAMC cells. PSTI also induced changes in vectorial ion transport (short-circuit current) when added to basolateral but not apical surfaces of polarized monolayers of Colony-29 cells. Restitution and vectorial ion transport effects of PSTI were dependent on the presence of a functioning epidermal growth factor (EGF) receptor because cells with a disrupted (EGFR(-/-) immortalized cells) or neutralized (EGFR blocking antibodies or tyrosine kinase inhibitor) receptor prevented these effects. PSTI also reduced the cytokine release of lipopolysaccharide-stimulated dendritic cells. We conclude that administration of PSTI may provide a novel method of stabilizing intestinal mucosa against noxious agents and stimulating repair after injury.
Tania Marchbank; Asif Mahmood; Anthony J Fitzgerald; Jan Domin; Matt Butler; Robert A Goodlad; George Elia; Helen M Cox; David A van Heel; Subrata Ghosh; Raymond J Playford
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  The American journal of pathology     Volume:  171     ISSN:  0002-9440     ISO Abbreviation:  Am. J. Pathol.     Publication Date:  2007 Nov 
Date Detail:
Created Date:  2007-11-05     Completed Date:  2008-01-25     Revised Date:  2014-02-19    
Medline Journal Info:
Nlm Unique ID:  0370502     Medline TA:  Am J Pathol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1462-73     Citation Subset:  AIM; IM    
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MeSH Terms
Carrier Proteins / biosynthesis,  genetics,  pharmacology*
Cell Line
Cell Movement
Cell Proliferation
Colitis / chemically induced,  pathology,  prevention & control
Dendritic Cells / physiology
Dextran Sulfate
Fatty Acid-Binding Proteins / genetics
Intestinal Mucosa / drug effects*,  physiology
Ion Transport
Jejunal Diseases / chemically induced,  metabolism,  pathology
Mice, Transgenic
Promoter Regions, Genetic
Rats, Sprague-Dawley
Receptor, Epidermal Growth Factor / metabolism
Recombinant Proteins / pharmacology
Grant Support
G0500936//Medical Research Council; //Wellcome Trust
Reg. No./Substance:
0/Carrier Proteins; 0/Fabp1 protein, rat; 0/Fatty Acid-Binding Proteins; 0/Recombinant Proteins; 0/SPINK1 protein, human; 9042-14-2/Dextran Sulfate; EC, Epidermal Growth Factor; XXE1CET956/Indomethacin

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