Section of Digestive Diseases and Nutrition

Chicago, IL, United States

Section of Digestive Diseases and Nutrition

Chicago, IL, United States
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Singla A.,University of Illinois at Chicago | Dwivedi A.,Section of Digestive Diseases and Nutrition | Saksena S.,Section of Digestive Diseases and Nutrition | Gill R.K.,Section of Digestive Diseases and Nutrition | And 5 more authors.
American Journal of Physiology - Gastrointestinal and Liver Physiology | Year: 2010

Lysophosphatidic acid (LPA), a potent bioactive phospholipid, is a natural component of food products like soy and egg yolk. LPA modulates a number of epithelial functions and has been shown to inhibit cholera toxin-induced diarrhea. Antidiarrheal effects of LPA are known to be mediated by inhibiting chloride secretion. However, the effects of LPA on chloride absorption in the mammalian intestine are not known. The present studies examined the effects of LPA on apical Cl-/OH- exchangers known to be involved in chloride absorption in intestinal epithelial cells. Caco-2 cells were treated with LPA, and Cl-/OH- exchange activity was measured as DIDS-sensitive 36Cl- uptake. Cell surface biotinylation studies were performed to evaluate the effect of LPA on cell surface levels of apical Cl -/OH- exchangers, downregulated in adenoma (DRA) (SLC26A3), and putative anion transporter-1 (SLC26A6). Treatment of Caco-2 cells with LPA (100 μM) significantly stimulated Cl-/OH- exchange activity. Specific agonist for LPA2 receptor mimicked the effects of LPA. LPA-mediated stimulation of Cl-/OH- exchange activity was dependent on activation of phosphatidylinositol 3-kinase/Akt signaling pathway. Consistent with the functional activity, LPA treatment resulted in increased levels of DRA on the apical membrane. Our results demonstrate that LPA stimulates apical Cl-/OH- exchange activity and surface levels of DRA in intestinal epithelial cells. This increase in Cl-/OH- exchange may contribute to the antidiarrheal effects of LPA. Copyright © 2010 the American Physiological Society.


Saksena S.,Section of Digestive Diseases and Nutrition | Goyal S.,Section of Digestive Diseases and Nutrition | Raheja G.,Section of Digestive Diseases and Nutrition | Singh V.,Section of Digestive Diseases and Nutrition | And 5 more authors.
American Journal of Physiology - Gastrointestinal and Liver Physiology | Year: 2011

P-glycoprotein (P-gp) mediates efflux of xenobiotics and bacterial toxins from the intestinal mucosa into the lumen. Dysregulation of P-gp has been implicated in inflammatory bowel disease. Certain probiotics have been shown to be effective in treating inflammatory bowel disease. However, direct effects of probiotics on P-gp are not known. Current studies examined the effects of Lactobacilli on P-gp function and expression in intestinal epithelial cells. Caco-2 monolayers and a mouse model of dextran sulfate sodium-induced colitis were utilized. P-gp activity was measured as verapamil-sensitive [3H]digoxin transepithelial flux. Multidrug resistant 1 (MDR1)/P-gp expression was measured by real-time quantitative PCR and immunoblotting. Culture supernatant (CS; 1:10 or 1:50, 24 h) of Lactobacillus acidophilus or Lactobacillus rhamnosus treatment of differentiated Caco-2 monolayers (21 days postplating) increased (~3-fold) MDR1/P-gp mRNA and protein levels. L. acidophilus or L. rhamnosus CS stimulated P-gp activity (~2-fold, P < 0.05) via phosphoinositide 3-kinase and ERK1/2 MAPK pathways. In mice, L. acidophilus or L. rhamnosus treatment (3 * 109 colonyforming units) increased mdr1a/P-gp mRNA and protein expression in the ileum and colon (2- to 3-fold). In the dextran sulfate sodium (DSS)-induced colitis model (3% DSS in drinking water for 7 days), the degree of colitis as judged by histological damage and myeloperoxidase activity was reduced by L. acidophilus. L. acidophilus treatment to DSS-treated mice blocked the reduced expression of mdr1a/ P-gp mRNA and protein in the distal colon. These findings suggest that Lactobacilli or their soluble factors stimulate P-gp expression and function under normal and inflammatory conditions. These data provide insights into a novel mechanism involving P-gp upregulation in beneficial effects of probiotics in intestinal inflammatory disorders. © 2011 by the American Physiological Society.

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