Bone marrow and non-bone marrow TLR4 regulates hepatic ischemia/reperfusion injury.
Hepatic ischemia-reperfusion injury (IRI) is a highly coordinated process often observed during liver transplantation, liver surgery, and hemorrhagic shock. Signaling through toll-like receptor 4 (TLR4), which is widely expressed on all kinds of liver cells, appears critical in the pathogenesis of IRI. Although the role of TLR4 expressed on non-parenchymal cells (NPCs) of the liver, including Kupffer cells and neutrophils, in IRI has been widely studied, TLR4 signaling on liver sinusoidal endothelial cells (LSECs) or hepatocytes in the process of IRI, and their coordination with bone marrow derived TLR4 in the late reperfusion stage, is largely unknown. We produced TLR4 chimeric mice that received hepatic IRI, and examined the degree of liver injury and the underlying mechanisms of injury. Results indicated that mutation of TLR4 on bone-marrow or non-bone marrow derived cells reduced hepatic IRI in the late reperfusion stage via cytokine release and neutrophil infiltration, while non-bone marrow derived TLR4 regulated the expression of ICAM-1 on hepatocytes and LSECs, exacerbating their injury. In conclusion, both TLR4 on bone marrow derived and non-bone marrow derived cells were necessary in the process of hepatic IRI.
Hui
Wang
W
Department of Medical Genetics, Tongji Medical College Affiliated to Huazhong University of Science and Technology, Wuhan 430030, People's Republic of China.
Jinxiang
Zhang
Z
Heshui
Wu
W
Zhuoya
Li
L
Qichang
Zheng
Z
D000818:Animals; D001853:Bone Marrow / Q000378:metabolism; D004195:Disease Models, Animal; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis; D053583:Interleukin-1beta / Q000096:biosynthesis; D008099:Liver / Q000098:blood supply*; D016031:Liver Transplantation; D051379:Mice; D008817:Mice, Mutant Strains; D009504:Neutrophils / Q000502:physiology; D015427:Reperfusion Injury / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D053583:Interleukin-1beta; D051197:Toll-Like Receptor 4; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1