Lactobacillus acidophilus stimulates the expression of SLC26A3 via a transcriptional mechanism.
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 ( approximately 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.
Raheja
Geetu
G
Department of Medicine, University of Illinois at Chicago and Jesse Brown Veterans Affairs Medical Center, 60612, USA.
Singh
Varsha
V
Ma
Ke
K
Boumendjel
Redouane
R
Borthakur
Alip
A
Gill
Ravinder K
RK
Saksena
Seema
S
Alrefai
Waddah A
WA
Ramaswamy
Krishnamurthy
K
Dudeja
Pradeep K
PK
D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid / Q000494:pharmacology; D000818:Animals; D017920:Antiporters / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D018938:Caco-2 Cells; D027963:Chloride-Bicarbonate Antiporters; D002712:Chlorides / Q000378:metabolism; D003106:Colon / Q000187:drug effects / Q000378:metabolism*; D015870:Gene Expression / Q000187:drug effects / Q000235:genetics*; D017930:Genes, Reporter / Q000235:genetics; D006801:Humans; D006878:Hydroxides / Q000378:metabolism; D007082:Ileum / Q000187:drug effects / Q000378:metabolism; D007583:Jejunum / Q000187:drug effects / Q000378:metabolism; D007779:Lactobacillus acidophilus; D026901:Membrane Transport Proteins / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D008840:Microfilament Proteins / Q000378:metabolism; D019936:Probiotics / Q000494:pharmacology*; D011401:Promoter Regions, Genetic / Q000235:genetics; D000076988:Sulfate Transporters; D014162:Transfection
D017920:Antiporters; D027963:Chloride-Bicarbonate Antiporters; D002712:Chlorides; D006878:Hydroxides; D026901:Membrane Transport Proteins; D008840:Microfilament Proteins; C081011:SLC26A3 protein, human; C439529:SLC26A6 protein, human; C489860:Slc26a3 protein, mouse; D000076988:Sulfate Transporters; C026615:villin; C031356:hydroxide ion; D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid