Pathogenic Escherichia roll increase Cl- secretion from intestinal epithelia by upregulating galanin-1 receptor expression

Gail Hecht, Jorge A. Marrero, Alexey Danilkovich, Kristina A. Matkowskyj, Suzanna D. Savkovic, Athanasia Koutsouris, Richard V. Benya

Research output: Contribution to journalArticle

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Abstract

Galanin is widely distributed in enteric nerve terminals lining the human gastrointestinal (GI) tract. We have shown previously that galanin-1 receptors (Gall-R) are expressed by epithelial cells lining the human GI tract, and upon activation cause Cl-secretion. Because expression of this receptor is transcriptionally regulated by nuclear factor-κB (NF-κB), which is activated by enteric pathogens as a part of the host epithelial response to infection, we investigated whether such bacterial pathogens could directly increase Gal1-R expression in the T84-cell model system. Pathogenic Escherichia coli, but not nonpathogenic E. coli, activate a p50/p65 NF-κB complex that binds to oligonucleotides corresponding to a recognition site located within the 5' flanking region of the human GAL1R gene. Pathogenic E. coli, but not normal commensal organisms, increase Gal1-R mRNA synthesis and [125I] galanin binding sites. Whereas galanin increases short-circuit current (Isc) approximately 5-fold in uninfected T84 cells, exposure to pathogenic, but not nonpathogenic, E. coli results in galanin increasing Isc approximately 20-fold. To confirm the validity of these in vitro observations, we also studied C57BL/6J mice infected with enterohemorrhagic E. coli (EHEC) by gavage. Infection caused a progressive increase in both NF- κB activation and Gal1-R expression, with maximal levels of both observed 3 days after gavage. Ussing chamber studies revealed that colons infected with EHEC, but not those exposed to normal colonic flora, markedly increased Isc in response to galanin. These data indicate that pathogen-induced increases in Gal1-R expression by epithelial cells lining the colon may represent a novel unifying pathway responsible for at least a portion of the excessive fluid secretion observed during infectious diarrhea.

Original languageEnglish (US)
Pages (from-to)253-262
Number of pages10
JournalJournal of Clinical Investigation
Volume104
Issue number3
StatePublished - Aug 1999

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Receptor, Galanin, Type 1
Galanin
Escherichia
Intestinal Mucosa
Escherichia coli
Enterohemorrhagic Escherichia coli
Gastrointestinal Tract
Colon
Epithelial Cells
Fluids and Secretions
5' Flanking Region
Infection
Inbred C57BL Mouse
Oligonucleotides
Diarrhea
Binding Sites
Messenger RNA
Genes

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Hecht, G., Marrero, J. A., Danilkovich, A., Matkowskyj, K. A., Savkovic, S. D., Koutsouris, A., & Benya, R. V. (1999). Pathogenic Escherichia roll increase Cl- secretion from intestinal epithelia by upregulating galanin-1 receptor expression. Journal of Clinical Investigation, 104(3), 253-262.

Pathogenic Escherichia roll increase Cl- secretion from intestinal epithelia by upregulating galanin-1 receptor expression. / Hecht, Gail; Marrero, Jorge A.; Danilkovich, Alexey; Matkowskyj, Kristina A.; Savkovic, Suzanna D.; Koutsouris, Athanasia; Benya, Richard V.

In: Journal of Clinical Investigation, Vol. 104, No. 3, 08.1999, p. 253-262.

Research output: Contribution to journalArticle

Hecht, G, Marrero, JA, Danilkovich, A, Matkowskyj, KA, Savkovic, SD, Koutsouris, A & Benya, RV 1999, 'Pathogenic Escherichia roll increase Cl- secretion from intestinal epithelia by upregulating galanin-1 receptor expression', Journal of Clinical Investigation, vol. 104, no. 3, pp. 253-262.
Hecht, Gail ; Marrero, Jorge A. ; Danilkovich, Alexey ; Matkowskyj, Kristina A. ; Savkovic, Suzanna D. ; Koutsouris, Athanasia ; Benya, Richard V. / Pathogenic Escherichia roll increase Cl- secretion from intestinal epithelia by upregulating galanin-1 receptor expression. In: Journal of Clinical Investigation. 1999 ; Vol. 104, No. 3. pp. 253-262.
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AU - Savkovic, Suzanna D.

AU - Koutsouris, Athanasia

AU - Benya, Richard V.

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