Galectin-3 Deficiency Facilitates TNF-α-Dependent Hepatocyte Death and Liver Inflammation in MCMV Infection.

Autor: Stojanovic B; Center for Molecular Medicine and Stem Cell Research, Faculty of Medical Sciences, University of Kragujevac, Kragujevac, Serbia.; Faculty of Medical Sciences, Institute of Pathophysiology, University of Kragujevac, Kragujevac, Serbia., Milovanovic J; Center for Molecular Medicine and Stem Cell Research, Faculty of Medical Sciences, University of Kragujevac, Kragujevac, Serbia.; Faculty of Medical Sciences, Institute of Histology, University of Kragujevac, Kragujevac, Serbia., Arsenijevic A; Center for Molecular Medicine and Stem Cell Research, Faculty of Medical Sciences, University of Kragujevac, Kragujevac, Serbia., Stojanovic B; Department of Surgery, Faculty of Medical Sciences, University of Kragujevac, Kragujevac, Serbia., Strazic Geljic I; Department for Histology and Embryology, Center for Proteomics, Faculty of Medicine, University of Rijeka, Rijeka, Croatia., Arsenijevic N; Center for Molecular Medicine and Stem Cell Research, Faculty of Medical Sciences, University of Kragujevac, Kragujevac, Serbia., Jonjic S; Department for Histology and Embryology, Center for Proteomics, Faculty of Medicine, University of Rijeka, Rijeka, Croatia., Lukic ML; Center for Molecular Medicine and Stem Cell Research, Faculty of Medical Sciences, University of Kragujevac, Kragujevac, Serbia., Milovanovic M; Center for Molecular Medicine and Stem Cell Research, Faculty of Medical Sciences, University of Kragujevac, Kragujevac, Serbia.
Jazyk: angličtina
Zdroj: Frontiers in microbiology [Front Microbiol] 2019 Feb 08; Vol. 10, pp. 185. Date of Electronic Publication: 2019 Feb 08 (Print Publication: 2019).
DOI: 10.3389/fmicb.2019.00185
Abstrakt: Galectin-3 (Gal-3) has a role in multiple inflammatory pathways. Various, opposite roles of Gal-3 in liver diseases have been described but there are no data about the role of Gal-3 in development of hepatitis induced with cytomegalovirus infection. In this study we aimed to clarify the role of Gal-3 in murine cytomegalovirus (MCMV)-induced hepatitis by using Gal-3-deficient (Gal-3 KO) mice. Here we provide the evidence that Gal-3 has the protective role in MCMV-induced hepatitis. Enhanced hepatitis manifested by more inflammatory and necrotic foci and serum level of ALT, enhanced apoptosis and necroptosis of hepatocytes and enhanced viral replication were detected in MCMV-infected Gal-3 deficient mice. NK cells does not contribute to more severe liver damage in MCMV-infected Gal-3 KO mice. Enhanced expression of TNF-α in the hepatocytes of Gal-3 KO mice after MCMV infection, abrogated hepatocyte death, and attenuated inflammation in the livers of Gal-3 KO mice after TNF-α blockade suggest that TNF-α plays the role in enhanced disease in Gal-3 deficient animals. Treatment with recombinant Gal-3 reduces inflammation and especially necrosis of hepatocytes in the livers of MCMV-infected Gal-3 KO mice. Our data highlight the protective role of Gal-3 in MCMV-induced hepatitis by attenuation of TNF-α-mediated death of hepatocytes.
Databáze: MEDLINE