Type I, but not type II, interferon is critical in liver injury induced after ischemia and reperfusion Export

@article{Zhai:2008p125, abstract = {We have documented the key role of toll-like receptor 4 (TLR4) activation and its signaling pathway mediated by interferon (IFN) regulatory factor 3, in the induction of inflammation leading to the hepatocellular damage during liver ischemia/reperfusion injury (IRI). Because type I IFN is the major downstream activation product of that pathway, we studied its role in comparison with IFN-gamma. Groups of type I (IFNAR), type II (IFNGR) IFN receptor-deficient mice, along with wild-type (WT) controls were subjected to partial liver warm ischemia (90 minutes) followed by reperfusion (1-6 hours). Interestingly, IFNAR knockout (KO) but not IFNGR KO mice were protected from IR-induced liver damage, as evidenced by decreased serum alanine aminotransferase and preservation of tissue architecture. IR-triggered intrahepatic pro-inflammatory response, assessed by tumor necrosis factor (TNF-alpha), interleukin 6 (IL-6), and chemokine (C-X-C motif) ligand 10 (CXCL-10) expression, was diminished selectively in IFNAR KO mice. Consistent with these findings, our in vitro cell culture studies have shown that: (1) although hepatocytes alone failed to respond to lipopolysaccharide (LPS), when co-cultured with macrophages they did respond to LPS via macrophage-derived IFN-beta; (2) macrophages required type I IFN to sustain CXCL10 production in response to LPS. This study documents that type I, but not type II, IFN pathway is required for IR-triggered liver inflammation/damage. Type I IFN mediates potential synergy between nonparenchyma and parenchyma cells in response to TLR4 activation.}, author = {Zhai, Yuan and Qiao, Bo and Gao, Feng and Shen, Xiuda and Vardanian, Andrew and Busuttil, Ronald W. and Jerzy}, citeulike-article-id = {3046191}, citeulike-linkout-0 = {http://www3.interscience.wiley.com/journal/116330117/abstract?CRETRY=1&SRETRY=0}, citeulike-linkout-1 = {http://dx.doi.org/10.1002/hep.21970}, doi = {10.1002/hep.21970}, journal = {Hepatology}, keywords = {4, animals, c57bl, carcinoma, cells, chemokine, cultured, cxcl10, diseases, file-import-08-07-27, hepatocellular, i, ii, inbred, injury, interferon, knockout, lipopolysaccharides, liver, macrophages, male, mice, neoplasms, receptor, reperfusion, signal, toll-like, transduction, type}, local-url = {file://localhost/Users/ken/Documents/Papers/2008/Zhai/Hepatology\%202008\%20Zhai.pdf}, month = {Jan}, number = {1}, pages = {199--206}, posted-at = {2008-07-27 14:46:03}, priority = {2}, title = {Type I, but not type II, interferon is critical in liver injury induced after ischemia and reperfusion}, url = {http://dx.doi.org/10.1002/hep.21970}, volume = {47}, year = {2008} }

TY - JOUR ID - Zhai:2008p125 L3 - citeulike-article-id:3046191 N2 - We have documented the key role of toll-like receptor 4 (TLR4) activation and its signaling pathway mediated by interferon (IFN) regulatory factor 3, in the induction of inflammation leading to the hepatocellular damage during liver ischemia/reperfusion injury (IRI). Because type I IFN is the major downstream activation product of that pathway, we studied its role in comparison with IFN-gamma. Groups of type I (IFNAR), type II (IFNGR) IFN receptor-deficient mice, along with wild-type (WT) controls were subjected to partial liver warm ischemia (90 minutes) followed by reperfusion (1-6 hours). Interestingly, IFNAR knockout (KO) but not IFNGR KO mice were protected from IR-induced liver damage, as evidenced by decreased serum alanine aminotransferase and preservation of tissue architecture. IR-triggered intrahepatic pro-inflammatory response, assessed by tumor necrosis factor (TNF-alpha), interleukin 6 (IL-6), and chemokine (C-X-C motif) ligand 10 (CXCL-10) expression, was diminished selectively in IFNAR KO mice. Consistent with these findings, our in vitro cell culture studies have shown that: (1) although hepatocytes alone failed to respond to lipopolysaccharide (LPS), when co-cultured with macrophages they did respond to LPS via macrophage-derived IFN-beta; (2) macrophages required type I IFN to sustain CXCL10 production in response to LPS. This study documents that type I, but not type II, IFN pathway is required for IR-triggered liver inflammation/damage. Type I IFN mediates potential synergy between nonparenchyma and parenchyma cells in response to TLR4 activation. IS - 1 JF - Hepatology EP - 206 TI - Type I, but not type II, interferon is critical in liver injury induced after ischemia and reperfusion VL - 47 SP - 199 KW - 4 KW - animals KW - c57bl KW - carcinoma KW - cells KW - chemokine KW - cultured KW - cxcl10 KW - diseases KW - file-import-08-07-27 KW - hepatocellular KW - i KW - ii KW - inbred KW - injury KW - interferon KW - knockout KW - lipopolysaccharides KW - liver KW - macrophages KW - male KW - mice KW - neoplasms KW - receptor KW - reperfusion KW - signal KW - toll-like KW - transduction KW - type AU - Zhai, Yuan AU - Qiao, Bo AU - Gao, Feng AU - Shen, Xiuda AU - Vardanian, Andrew AU - Busuttil, Ronald AU - Jerzy PY - 2008/Jan// UR - http://dx.doi.org/10.1002/hep.21970 ER -