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Gastroenterology Commons

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Signal Transduction

Articles, Abstracts, and Reports

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Full-Text Articles in Gastroenterology

Macrophage-Derived Il-1Β/Nf-Κb Signaling Mediates Parenteral Nutrition-Associated Cholestasis., Karim C El Kasmi, Padade M Vue, Aimee L Anderson, Michael W Devereaux, Swati Ghosh, Natarajan Balasubramaniyan, Sophie A Fillon, Carola Dahrenmoeller, Ayed Allawzi, Crystal Woods, Sarah Mckenna, Clyde J Wright, Linda Johnson, Angelo D'Alessandro, Julie A Reisz, Eva Nozik-Grayck, Frederick J Suchy, Ronald J Sokol Apr 2018

Macrophage-Derived Il-1Β/Nf-Κb Signaling Mediates Parenteral Nutrition-Associated Cholestasis., Karim C El Kasmi, Padade M Vue, Aimee L Anderson, Michael W Devereaux, Swati Ghosh, Natarajan Balasubramaniyan, Sophie A Fillon, Carola Dahrenmoeller, Ayed Allawzi, Crystal Woods, Sarah Mckenna, Clyde J Wright, Linda Johnson, Angelo D'Alessandro, Julie A Reisz, Eva Nozik-Grayck, Frederick J Suchy, Ronald J Sokol

Articles, Abstracts, and Reports

In infants intolerant of enteral feeding because of intestinal disease, parenteral nutrition may be associated with cholestasis, which can progress to end-stage liver disease. Here we show the function of hepatic macrophages and phytosterols in parenteral nutrition-associated cholestasis (PNAC) pathogenesis using a mouse model that recapitulates the human pathophysiology and combines intestinal injury with parenteral nutrition. We combine genetic, molecular, and pharmacological approaches to identify an essential function of hepatic macrophages and IL-1β in PNAC. Pharmacological antagonism of IL-1 signaling or genetic deficiency in CCR2, caspase-1 and caspase-11, or IL-1 receptor (which binds both IL-1α and IL-1β) prevents PNAC in …