Lactobacillus acidophilus stimulates the expression of SLC26A3 via a transcriptional mechanism

Geetu Raheja, Varsha Singh, Ke Ma, Redouane Boumendjel, Alip Borthakur, Ravinder K. Gill, Seema Saksena, Waddah A. Alrefai, Krishnamurthy Ramaswamy, Pradeep K. Dudeja

Research output: Contribution to journalArticle

Abstract

Clinical efficacy of probiotics in treating various forms of diarrhea has been clearly established. However, mechanisms underlying antidiarrheal effects of probiotics are not completely defined. Diarrhea is caused either by decreased absorption or increased secretion of electrolytes and solutes in the intestine. In this regard, the electroneutral absorption of two major electrolytes, Na+ and Cl-, occurs mainly through the coupled operation of Na+/H+ exchangers and Cl-/OH- exchangers. Previous studies from our laboratory have shown that Lactobacillus acidophilus (LA) acutely stimulated Cl-/OH- exchange activity via an increase in the surface levels of the apical anion exchanger SLC26A3 (DRA). However, whether probiotics influence SLC26A3 expression and promoter activity has not been examined. The present studies were, therefore, undertaken to investigate the long-term effects of LA on SLC26A3 expression and promoter activity. Treatment of Caco-2 cells with LA for 6-24 h resulted in a significant increase in Cl-/OH- exchange activity. DRA mRNA levels were also significantly elevated in response to LA treatment starting as early as 8 h. Additionally, the promoter activity of DRA was increased by more than twofold following 8 h LA treatment of Caco-2 cells. Similar to the in vitro studies, in vivo studies using mice gavaged with LA also showed significantly increased DRA mRNA (∼4-fold) and protein expression in the colonic regions as assessed by Western blot analysis and immunofluorescence. In conclusion, increase in DRA promoter activity and expression may contribute to the upregulation of intestinal electrolyte absorption and might underlie the potential antidiarrheal effects of LA.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Gastrointestinal and Liver Physiology
Volume298
Issue number3
DOIs
StatePublished - Mar 2010
Externally publishedYes

Fingerprint

Lactobacillus acidophilus
Probiotics
Electrolytes
Antidiarrheals
Caco-2 Cells
Diarrhea
Messenger RNA
Sodium-Hydrogen Antiporter
Intestinal Absorption
Intestines
Fluorescent Antibody Technique
Anions
Up-Regulation
Therapeutics
Western Blotting

Keywords

  • Caco-2; DRA (downregulated in adenoma)
  • Diarrhea
  • Probiotics

ASJC Scopus subject areas

  • Gastroenterology
  • Physiology (medical)
  • Physiology
  • Hepatology

Cite this

Lactobacillus acidophilus stimulates the expression of SLC26A3 via a transcriptional mechanism. / Raheja, Geetu; Singh, Varsha; Ma, Ke; Boumendjel, Redouane; Borthakur, Alip; Gill, Ravinder K.; Saksena, Seema; Alrefai, Waddah A.; Ramaswamy, Krishnamurthy; Dudeja, Pradeep K.

In: American Journal of Physiology - Gastrointestinal and Liver Physiology, Vol. 298, No. 3, 03.2010.

Research output: Contribution to journalArticle

Raheja, Geetu ; Singh, Varsha ; Ma, Ke ; Boumendjel, Redouane ; Borthakur, Alip ; Gill, Ravinder K. ; Saksena, Seema ; Alrefai, Waddah A. ; Ramaswamy, Krishnamurthy ; Dudeja, Pradeep K. / Lactobacillus acidophilus stimulates the expression of SLC26A3 via a transcriptional mechanism. In: American Journal of Physiology - Gastrointestinal and Liver Physiology. 2010 ; Vol. 298, No. 3.
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AB - Clinical efficacy of probiotics in treating various forms of diarrhea has been clearly established. However, mechanisms underlying antidiarrheal effects of probiotics are not completely defined. Diarrhea is caused either by decreased absorption or increased secretion of electrolytes and solutes in the intestine. In this regard, the electroneutral absorption of two major electrolytes, Na+ and Cl-, occurs mainly through the coupled operation of Na+/H+ exchangers and Cl-/OH- exchangers. Previous studies from our laboratory have shown that Lactobacillus acidophilus (LA) acutely stimulated Cl-/OH- exchange activity via an increase in the surface levels of the apical anion exchanger SLC26A3 (DRA). However, whether probiotics influence SLC26A3 expression and promoter activity has not been examined. The present studies were, therefore, undertaken to investigate the long-term effects of LA on SLC26A3 expression and promoter activity. Treatment of Caco-2 cells with LA for 6-24 h resulted in a significant increase in Cl-/OH- exchange activity. DRA mRNA levels were also significantly elevated in response to LA treatment starting as early as 8 h. Additionally, the promoter activity of DRA was increased by more than twofold following 8 h LA treatment of Caco-2 cells. Similar to the in vitro studies, in vivo studies using mice gavaged with LA also showed significantly increased DRA mRNA (∼4-fold) and protein expression in the colonic regions as assessed by Western blot analysis and immunofluorescence. In conclusion, increase in DRA promoter activity and expression may contribute to the upregulation of intestinal electrolyte absorption and might underlie the potential antidiarrheal effects of LA.

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