Marshall Digital Scholar

Title

Enteropathogenic Escherichia coli infection inhibits intestinal serotonin transporter function and expression

Authors

Ali Esmaili
Saad F. Nazir
Alip Borthakur, Marshall UniversityFollow
Dan Yu
Jerrold R. Turner
Seema Saksema
Amika Singla
Gail A. Hecht
Waddah A. Alrefai
Ravinder K. Gill

Document Type

Article

Publication Date

12-2009

Abstract

Background & Aims: Serotonin transporter (SERT) plays a critical role in regulating serotonin (5-hydroxytryptamine [5-HT]) availability in the gut. Elevated 5-HT levels are associated with diarrheal conditions such as irritable bowel syndrome and enteric infections. Whether alteration in SERT activity contributes to the pathophysiology of diarrhea induced by the food-borne pathogen enteropathogenic Escherichia coli (EPEC) is not known. The present studies examined the effects of EPEC infection on SERT activity and expression in intestinal epithelial cells and elucidated the underlying mechanisms.

Methods: Caco-2 cells as a model of human intestinal epithelia and EPEC-infected C57BL/6J mouse model of infection were utilized. SERT activity was measured as Na+ and Cl− dependent 3[H] 5-HT uptake. SERT expression was measured by real-time quantitative reverse-transcription polymerase chain reaction, Western blotting, and immunofluorescence studies.

Results: Infection of Caco-2 cells with EPEC for 30–120 minutes decreased apical SERT activity (P < .001) in a type 3 secretion system dependent manner and via involvement of protein tyrosine phosphatases. EPEC infection decreased Vmax of the transporter; whereas cell surface biotinylation studies revealed no alteration in the cellular or plasma membrane content of SERT in Caco-2 cells. EPEC infection of mice (24 hours) reduced SERT immunostaining with a corresponding decrease in SERT messenger RNA levels, 5-HT uptake, and mucosal 5-HT content in the small intestine.

Conclusions: Our results demonstrate inhibition of SERT by EPEC and define the mechanisms underlying these effects. These data may aid in the development of a novel pharmacotherapy to modulate the serotonergic system in treatment of infectious diarrheal diseases.

Comments

Copyright © 2009 by the AGA Institute.

Recommended Citation

Esmaili A, Nazir SF, Borthakur A, Yu D, Turner JR, Saksena S, Singla A, Hecht GA, Alrefai WA, Gill RK. Enteropathogenic Escherichia coli infection inhibits intestinal serotonin transporter function and expression. Gastroenterology. 2009;137(6):2074-83.