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Full-Text Articles in Medicine and Health Sciences
Type I Interferons Protect From Toll-Like Receptor 9-Associated Liver Injury And Regulate Il-1 Receptor Antagonist In Mice, Jan Petrasek, Angela Dolganiuc, Timea Csak, Evelyn Kurt-Jones, Gyongyi Szabo
Type I Interferons Protect From Toll-Like Receptor 9-Associated Liver Injury And Regulate Il-1 Receptor Antagonist In Mice, Jan Petrasek, Angela Dolganiuc, Timea Csak, Evelyn Kurt-Jones, Gyongyi Szabo
Gyongyi Szabo
BACKGROUND and AIMS: Liver inflammation and injury are mediated by the innate immune response, which is regulated by Toll-like receptors (TLR). Activation of TLR9 induces type I interferons (IFNs) via the interferon regulatory factor (IRF)-7. We investigated the roles of type I IFNs in TLR9-associated liver injury. METHODS: Wild-type (WT), IRF7-deficient, and IFN-alpha/beta receptor 1 (IFNAR1)-deficient mice were stimulated with TLR9 or TLR2 ligands. Findings from mice were verified in cultured hepatocytes and liver mononuclear cells (LMNCs) as well as in vivo experiments using recombinant type I IFN and interleukin-1 receptor antagonist (IL-1ra). RESULTS: Type I IFNs were up-regulated during …
Interferon Regulatory Factor 3 And Type I Interferons Are Protective In Alcoholic Liver Injury In Mice By Way Of Crosstalk Of Parenchymal And Myeloid Cells, Jan Petrasek, Angela Dolganiuc, Timea Csak, Bharath Nath, Istvan Hritz, Karen Kodys, Donna Catalano, Evelyn Kurt-Jones, Pranoti Mandrekar, Gyongyi Szabo
Interferon Regulatory Factor 3 And Type I Interferons Are Protective In Alcoholic Liver Injury In Mice By Way Of Crosstalk Of Parenchymal And Myeloid Cells, Jan Petrasek, Angela Dolganiuc, Timea Csak, Bharath Nath, Istvan Hritz, Karen Kodys, Donna Catalano, Evelyn Kurt-Jones, Pranoti Mandrekar, Gyongyi Szabo
Gyongyi Szabo
Alcoholic liver disease (ALD) features increased hepatic exposure to bacterial lipopolysaccharide (LPS). Toll-like receptor-4 (TLR4) recognizes LPS and activates signaling pathways depending on MyD88 or TRIF adaptors. We previously showed that MyD88 is dispensable in ALD. TLR4 induces Type I interferons (IFNs) in an MyD88-independent manner that involves interferon regulatory factor-3 (IRF3). We fed alcohol or control diets to wild-type (WT) and IRF3 knock-out (KO) mice, and to mice with selective IRF3 deficiency in liver parenchymal and bone marrow-derived cells. Whole-body IRF3-KO mice were protected from alcohol-induced liver injury, steatosis, and inflammation. In contrast to WT or bone marrow-specific IRF3-KO …
Innate Immunity And Alcoholic Liver Disease, Bin Gao, Ekihiro Seki, Jessica Cohen, Laura Nagy, Gyongyi Szabo, Samir Zakhari
Innate Immunity And Alcoholic Liver Disease, Bin Gao, Ekihiro Seki, Jessica Cohen, Laura Nagy, Gyongyi Szabo, Samir Zakhari
Gyongyi Szabo
Excessive alcohol consumption is a leading cause of chronic liver disease in the Western world. Alcohol-induced hepatotoxicity and oxidative stress are important mechanisms contributing to the pathogenesis of alcoholic liver disease. However, emerging evidence suggests that activation of innate immunity involving TLR4 and complement also plays an important role in initiating alcoholic steatohepatitis and fibrosis, but the role of adaptive immunity in the pathogenesis of alcoholic liver disease remains obscure. Activation of a TLR4-mediated MyD88-independent (TRIF/IRF-3) signaling pathway in Kupffer cells contributes to alcoholic steatohepatitis, while activation of TLR4 signaling in hepatic stellate cells promotes liver fibrosis. Alcohol consumption activates …