Lactobacillus acidophilus attenuates downregulation of DRA function and expression in inflammatory models

Am J Physiol Gastrointest Liver Physiol. 2014 Sep 15;307(6):G623-31. doi: 10.1152/ajpgi.00104.2014. Epub 2014 Jul 24.

Abstract

Probiotics, including Lactobacilli, are commensal bacteria that have been used in clinical trials and experimental models for the prevention and treatment of diarrheal disorders. Our previous studies have shown that Lactobacillus acidophilus (LA) and its culture supernatant (CS) stimulated Cl(-)/HCO3 (-) exchange activity, acutely via an increase in the surface levels of downregulated in adenoma (DRA, SLC26A3) and in long-term treatments via increasing its expression involving transcriptional mechanisms. However, the role of LA in modulating DRA activity under inflammatory conditions is not known. Current in vitro studies using human intestinal epithelial Caco-2 cells examined the efficacy of LA or its CS in counteracting the inhibitory effects of interferon-γ (IFN-γ) on Cl(-)/HCO3 (-) exchange activity. Pretreatment of cells with LA or LA-CS for 1 h followed by coincubation with IFN-γ significantly alleviated the inhibitory effects of IFN-γ on Cl(-)/HCO3 (-) exchange activity. In the in vivo model of dextran sulfate sodium-induced experimental colitis (3% in drinking water for 7 days) in C57BL/6J mice, administration of live LA (3 × 10(9) colony-forming units) via oral gavage attenuated colonic inflammation. LA administration also counteracted the colitis-induced decrease in DRA mRNA and protein levels. Efficacy of LA or its secreted soluble factors in alleviating inflammation and inflammation-associated dysregulation of DRA activity could justify their therapeutic potential in inflammatory diarrheal diseases.

Keywords: Caco-2; dextran sulfate sodium; diarrhea; downregulated in adenoma; interferon-γ; probiotics.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Antiporters / genetics
  • Antiporters / metabolism*
  • Caco-2 Cells
  • Chloride-Bicarbonate Antiporters / genetics
  • Chloride-Bicarbonate Antiporters / metabolism*
  • Colitis / genetics
  • Colitis / immunology
  • Colitis / metabolism
  • Colitis / microbiology
  • Colitis / prevention & control*
  • Colon / immunology
  • Colon / metabolism*
  • Colon / microbiology*
  • Dextran Sulfate
  • Diarrhea / metabolism
  • Diarrhea / microbiology
  • Diarrhea / prevention & control
  • Disease Models, Animal
  • Down-Regulation
  • Humans
  • Inflammation Mediators / metabolism
  • Interferon-gamma / metabolism
  • Lactobacillus acidophilus / growth & development*
  • Lactobacillus acidophilus / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Probiotics*
  • Promoter Regions, Genetic
  • RNA, Messenger / metabolism
  • Sulfate Transporters
  • Time Factors
  • Transcription, Genetic
  • Transfection
  • Weight Loss

Substances

  • Antiporters
  • Chloride-Bicarbonate Antiporters
  • Inflammation Mediators
  • RNA, Messenger
  • SLC26A3 protein, human
  • Slc26a3 protein, mouse
  • Sulfate Transporters
  • Interferon-gamma
  • Dextran Sulfate