RESUMO
Triptolide (TP) induces severe liver injury, but its hepatotoxicity mechanisms are still unclear. Inflammatory responses may be involved in the pathophysiology. Neutrophils are the first-line immune effectors for sterile and non-sterile inflammatory responses. Thus, the aim of the present study was to investigate the neutrophilic inflammatory response in TP-induced liver injury in C57BL/6 mice. Our results showed that neutrophils were recruited and accumulated in the liver, which was parallel to or slightly after the development of liver injury. Neutrophils induced release of myeloperoxidase and up-regulation of CD11b, which caused cytotoxicity and hepatocyte death. Hepatic expressions of CXL1, TNF-α, IL-6, and MCP1 were increased significantly to regulate neutrophils recruitment and activation. Up-regulation of toll like receptors 4 and 9 also facilitated neutrophils infiltration. Moreover, neutrophils depletion using an anti-Gr1 antibody showed mild protection against TP overdose. These results indicated that neutrophils accumulation might be the secondary response, not the cause of TP-induced liver injury. In conclusion, the inflammatory response including neutrophil infiltration may play a role in TP-induced hepatotoxicity, but may not be severe enough to cause additional liver injury.
Assuntos
Animais , Feminino , Humanos , Camundongos , Doença Hepática Induzida por Substâncias e Drogas , Alergia e Imunologia , Quimiocina CCL2 , Genética , Alergia e Imunologia , Diterpenos , Medicamentos de Ervas Chinesas , Compostos de Epóxi , Interleucina-6 , Genética , Alergia e Imunologia , Peptídeos e Proteínas de Sinalização Intracelular , Genética , Alergia e Imunologia , Fígado , Alergia e Imunologia , Camundongos Endogâmicos C57BL , Infiltração de Neutrófilos , Neutrófilos , Alergia e Imunologia , Fenantrenos , Tripterygium , Química , Fator de Necrose Tumoral alfa , Genética , Alergia e ImunologiaRESUMO
Triptolide (TP) induces severe liver injury, but its hepatotoxicity mechanisms are still unclear. Inflammatory responses may be involved in the pathophysiology. Neutrophils are the first-line immune effectors for sterile and non-sterile inflammatory responses. Thus, the aim of the present study was to investigate the neutrophilic inflammatory response in TP-induced liver injury in C57BL/6 mice. Our results showed that neutrophils were recruited and accumulated in the liver, which was parallel to or slightly after the development of liver injury. Neutrophils induced release of myeloperoxidase and up-regulation of CD11b, which caused cytotoxicity and hepatocyte death. Hepatic expressions of CXL1, TNF-α, IL-6, and MCP1 were increased significantly to regulate neutrophils recruitment and activation. Up-regulation of toll like receptors 4 and 9 also facilitated neutrophils infiltration. Moreover, neutrophils depletion using an anti-Gr1 antibody showed mild protection against TP overdose. These results indicated that neutrophils accumulation might be the secondary response, not the cause of TP-induced liver injury. In conclusion, the inflammatory response including neutrophil infiltration may play a role in TP-induced hepatotoxicity, but may not be severe enough to cause additional liver injury.