title: Lactoferrin ameliorates prostaglandin E2-mediated inhibition of Na+ -glucose cotransport in enterocytes.
abstract: Various immunoinflammatory cytokines are produced during chronic intestinal inflammation, which inhibits Na(+)-glucose cotransport (SGLT1) in villus cells. Lactoferrin (Lf), abundantly present in colostrum, is a multifunctional glycoprotein that is absorbed by receptor-mediated transcytosis in humans and animals and has been shown to exert anti-inflammatory effects. Therefore, this study aimed to examine whether Lf would prevent PGE2 effect on SGLT1 for glucose absorption in enterocytes. Intestinal epithelial cells (IEC-6) were grown on transwell plates, treated with phlorizin, PGE2, AH6809, and Lf, and 3-O-methyl d-glucopyranose (OMG) uptake was measured in 10 days postconfluent. Na(+)-dependent OMG uptake, phlorizin, and immunoblotting studies established the activity and apical membrane localization of SGLT1 in IEC-6 cells. PGE2 inhibited SGLT1 in a concentration- and time-dependent manner with an inhibitory constant (Ki) of 50.0 nmol/L and that was antagonized by prostanoid receptor inhibitor, AH6809. PGE2 did not alter Na(+)/K(+)-ATPase activity. In contrast, quantitative real-time polymerase chain reaction and Western blot analyses revealed that SGLT1-specific transcripts and protein expression level were decreased 3-fold by PGE2. Furthermore, PGE2 treatment increased intracellular cyclic adenosine monophosphate (cAMP) and Ca(2+) concentrations and decreased SGLT1 expression on the apical membrane, and these effects were ameliorated by Lf. Therefore, we conclude that Lf ameliorates the PGE2 inhibition of SGLT1 most likely via the Ca(2+)- and cAMP-signaling pathways.
authors.affiliation: Department of Biology, LeMoyne-Owen College, 807 Walker Avenue, Memphis, TN 38126, USA.
authors.forename: Jamilur R
authors.initials: JR
authors.lastname: Talukder
authors.forename: Ashley
authors.initials: A
authors.lastname: Griffin
authors.forename: Antara
authors.initials: A
authors.lastname: Jaima
authors.forename: Brittney
authors.initials: B
authors.lastname: Boyd
authors.forename: Jaleesa
authors.initials: J
authors.lastname: Wright
mesh_terms: D000818:Animals; D017209:Apoptosis; D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D015232:Dinoprostone / Q000378:metabolism* / Q000494:pharmacology; D020895:Enterocytes / Q000187:drug effects / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism*; D017136:Ion Transport; D007781:Lactoferrin / Q000378:metabolism* / Q000494:pharmacology; D051381:Rats; D058306:Receptors, Prostaglandin E, EP1 Subtype / Q000378:metabolism; D058307:Receptors, Prostaglandin E, EP2 Subtype / Q000378:metabolism; D015398:Signal Transduction; D012964:Sodium / Q000378:metabolism*; D051269:Sodium-Glucose Transporter 1 / Q000378:metabolism*; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism
chemical_list: D058306:Receptors, Prostaglandin E, EP1 Subtype; D058307:Receptors, Prostaglandin E, EP2 Subtype; D051269:Sodium-Glucose Transporter 1; D012964:Sodium; D007781:Lactoferrin; D000254:Sodium-Potassium-Exchanging ATPase; D005947:Glucose; D015232:Dinoprostone; D002118:Calcium