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Full-Text Articles in Molecular Biology
Endoplasmic Reticulum Stress-Induced Hepatocellular Death Pathways Mediate Liver Injury And Fibrosis Via Stimulator Of Interferon Genes., Arvin Iracheta-Vellve, Jan Petrasek, Benedek Gyongyosi, Abhishek Satishchandran, Patrick Lowe, Karen Kodys, Donna Catalano, Charles D. Calenda, Evelyn A. Kurt-Jones, Kate A. Fitzgerald, Gyongyi Szabo
Endoplasmic Reticulum Stress-Induced Hepatocellular Death Pathways Mediate Liver Injury And Fibrosis Via Stimulator Of Interferon Genes., Arvin Iracheta-Vellve, Jan Petrasek, Benedek Gyongyosi, Abhishek Satishchandran, Patrick Lowe, Karen Kodys, Donna Catalano, Charles D. Calenda, Evelyn A. Kurt-Jones, Kate A. Fitzgerald, Gyongyi Szabo
Katherine A. Fitzgerald
Fibrosis, driven by inflammation, marks the transition from benign to progressive stages of chronic liver diseases. Although inflammation promotes fibrogenesis, it is not known whether other events, such as hepatocyte death, are required for the development of fibrosis. Interferon Regulatory Factor 3 (IRF3) regulates hepatocyte apoptosis and production of Type-I interferons (IFNs). In the liver, IRF3 is activated via Toll-like receptor 4 (TLR4) signaling or the ER adapter, Stimulator of Interferon Genes (STING). We hypothesized that IRF3-mediated hepatocyte death is an independent determinant of chemically-induced liver fibrogenesis. To test this, we performed acute or chronic carbontetrachloride (CCl4) administration to WT, …
Caspase-8 Scaffolding Function And Mlkl Regulate Nlrp3 Inflammasome Activation Downstream Of Tlr3, Seokwon Kang, Teresa Fernandes-Alnemri, Corey Rogers, Lindsey Mayes, Ying Wang, Christopher P. Dillon, Linda Roback, William Kaiser, Andrew Oberst, Junji Sagara, Katherine A. Fitzgerald, Douglas R. Green, Jianke Zhang, Edward S. Mocarski, Emad S. Alnemri
Caspase-8 Scaffolding Function And Mlkl Regulate Nlrp3 Inflammasome Activation Downstream Of Tlr3, Seokwon Kang, Teresa Fernandes-Alnemri, Corey Rogers, Lindsey Mayes, Ying Wang, Christopher P. Dillon, Linda Roback, William Kaiser, Andrew Oberst, Junji Sagara, Katherine A. Fitzgerald, Douglas R. Green, Jianke Zhang, Edward S. Mocarski, Emad S. Alnemri
Katherine A. Fitzgerald
TLR2 promotes NLRP3 inflammasome activation via an early MyD88-IRAK1-dependent pathway that provides a priming signal (signal 1) necessary for activation of the inflammasome by a second potassium-depleting signal (signal 2). Here we show that TLR3 binding to dsRNA promotes post-translational inflammasome activation through intermediate and late TRIF/RIPK1/FADD-dependent pathways. Both pathways require the scaffolding but not the catalytic function of caspase-8 or RIPK1. Only the late pathway requires kinase competent RIPK3 and MLKL function. Mechanistically, FADD/caspase-8 scaffolding function provides a post-translational signal 1 in the intermediate pathway, whereas in the late pathway it helps the oligomerization of RIPK3, which together with …