Loss of interleukin-12 modifies the pro-inflammatory response but does not prevent duct obstruction in experimental biliary atresia.

BMC Gastroenterology
Sujit K MohantyJorge Bezerra

Abstract

Livers of infants with biliary atresia and of neonatal mice infected with rotavirus (RRV) have increased expression of interferon-gamma (IFNgamma) and interleukin (IL)-12. While the expression of IFNgamma regulates the obstruction of extrahepatic bile ducts by lymphocytes, the role of IL-12 in the pathogenesis of biliary obstruction is unknown. Based on the role of IL-12 as a key proinflammatory cytokine, we hypothesized that loss of IL-12 prevents the obstruction of extrahepatic bile ducts. IL12-knockout (IL-12KO) and wild type mice were injected with RRV or saline at day 1 of age and monitored for the development of symptoms. The cellular and molecular phenotypes were determined at days 3, 7, and 14 by real-time PCR and flow cytometry. RRV infection of IL-12KO mice resulted in growth failure, jaundice/acholic stools, and decreased survival similar to wild-type mice. IL-12KO mice had a remarkable neutrophil-rich portal inflammation and epithelial sloughing of extrahepatic bile ducts. Loss of IL-12 decreased but did not abolish the hepatic expression of IFNgamma, displayed a remarkable increase in expression of TNFalpha, IFNalpha, IFNbeta and decreased expression of IL-4 and IL-5. Loss of IL-12 did not modify the progression of...Continue Reading

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Citations

Feb 12, 2013·Seminars in Liver Disease·Cara L MackRonald J Sokol
Oct 19, 2011·The Journal of Clinical Investigation·Jun LiJorge A Bezerra
Aug 31, 2013·Orphanet Journal of Rare Diseases·Claus Petersen, Mark Davenport
Jan 14, 2011·Annual Review of Medicine·Kazuhiko Bessho, Jorge A Bezerra
Nov 18, 2008·Expert Opinion on Investigational Drugs·Barbara A HaberKathleen M Loomes
May 27, 2015·Nature Reviews. Gastroenterology & Hepatology·Akihiro AsaiJorge A Bezerra
Nov 14, 2008·Journal of Cellular Physiology·Katherine J MotylLaura R McCabe
Mar 24, 2009·Journal of Pediatric Surgery·Mubeen JafriGreg Tiao
Jul 18, 2012·Seminars in Pediatric Surgery·Claus Petersen
Apr 9, 2008·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Nissa EricksonJorge A Bezerra
Sep 5, 2014·Clinical Pediatrics·Dong ZhaoQiang Xia
Sep 21, 2018·Journal of Virology·Holly TurulaChristiane E Wobus
Oct 14, 2016·American Journal of Physiology. Regulatory, Integrative and Comparative Physiology·Regina IrwinLaura R McCabe
Nov 30, 2011·Current Opinion in Gastroenterology·Paula M Hertel, Mary K Estes
Apr 4, 2018·Innovative Surgical Sciences·Claus Petersen, Omid Madadi-Sanjani
Jun 11, 2020·Future Science OA·Mukul Vij, Mohamed Rela

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Methods Mentioned

BETA
dissecting
electrophoresis
PCR
FACS
FCS
flow cytometry

Software Mentioned

CellQuest

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