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1篇 您的检索式:作者名="Brendan Ferraro"
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1Sieving characteristics of cytokine-and peroxide-induced epithelial barrier leak:Inhibition by berberine显示文摘AIM:To study whether the inflammatory bowel disease(IBD)colon which exhibits varying severity and cytokine levels across its mucosa create varying types of transepithelial leak.METHODS:We examined the effects of tumor necrosis factor-α(TNF-α),interferon-γ(IFN-γ),interleukin-1-β(IL1β)and hydrogen peroxide(H_2O_2)-singly and in combinations-on barrier function of CACO-2 cell layers.Our focus was on the type(not simply the magnitude)of transepithelial leak generated by these agents as measured by transepithelial electrical resistance(TER)and transepithelial flux of ^(14)C-D-mannitol,3H-Lactulose and ^(14)C-Polyethylene glycol as radiolabeled probe molecules.The isoquinoline alkaloid,berberine,was then examined for its ability to reduce specific types of transepithelial leak.RESULTS:Exposure to TNF-α alone(200 ng/mL;48 h)induced a 50% decrease in TER,i.e.,increased leak of Na^+ and Cl--with only a marginal but statistically significant increase in transepithelial leak of ^(14)C-mannitol(Jm).Exposure to TNF-α + IFN-γ(200 ng/mL;48 h)+ IL1β(50 ng/mL;48 h)did not increase the TER change(from TNF-α alone),but there was now a 100% increase in J_m.There however was no increase in transepithelial leak of two larger probe molecules,~3H-lactulose and ^(14)C-polyethylene glycol(PEG).However,exposure to TNF-α + IFN-γ + IL1β followed by a 5 h exposure to2 mmol/L H_2O_2 resulted in a 500% increase in ^(14)C-PEG leak as well as leak to the luminal mitogen,epidermal growth factor.CONCLUSION:This model of graded transepithelial leak is useful in evaluating therapeutic agents reducing IBD morbidity by reducing barrier leak to various luminal substances.Katherine M DiGuilio Christina M Mercogliano Jillian Born Brendan Ferraro Julie To Brittany Mixson Allison Smith Mary Carmen Valenzano James M Mullin 2016World Journal of Gastrointestinal Pathophysiology2016,7,2:6
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