Little is known about the mechanism and signal transduction by LPS-mediated immunomodulation of murine peritoneal macrophages. It is found that the signal molecules of the down-stream of Ras, Raf-1, MAPK p44, and MAPK...Little is known about the mechanism and signal transduction by LPS-mediated immunomodulation of murine peritoneal macrophages. It is found that the signal molecules of the down-stream of Ras, Raf-1, MAPK p44, and MAPK p42 are phosphorylated, and cPLA2 is activated with a significant increase of the release of [ H3 ] AA by macrophages in response to LPS and PMA. Compared with the very recent finding that LPS and PMA trigger the activation and translocation of PKC-α and PKC-ε, these findings suggest that there is a connection between PKC signaling pathway and the Raf-1/MAPK pathway and that the activation of these main signaling events may be closely related to the secretion of IL-12 during LPS-induced modulation of macrophages.展开更多
Since cell signal transduction plays an important role in disclosing the nature of human diseases, the pathogenesis of viruses may result from the disturbance of intracellular signal cascades caused by viral proteins....Since cell signal transduction plays an important role in disclosing the nature of human diseases, the pathogenesis of viruses may result from the disturbance of intracellular signal cascades caused by viral proteins. Hepatitis C virus (HCV) is a main causative agent of severe human liver disorders worldwide. So far, the mechanisms of HCV pathogenicity remain unclear. Envelope protein 2 (E2) of HCV is thought to be responsible for initiating virus attachment to host cells, which is a prerequisite of HCV infection. We assume that some early events of HCV pathogenic effects may result from the interaction of HCV E2 protein with its cellular receptor (human CD81), which could regulate cell proliferation and differentiation. To test this hypothesis, the effects of HCV E2 protein on MAPK/ERK pathway in Molt-4 and U937 cells with or without human CD81 expression were investigated. The results showed that HCV E2 protein could specifically activate the MAPK/ERK pathway, and such activation was inhibited by monoclonal antibodies against CD81 or HCV E2, serum antibodies from HCV infected patients, and upstream MEK1 inhibitor PD98059. Moreover, HCV E2-driven MAPK/ERK or downstream transcription factor Elk-1 activation was completely blocked in the presence of PD98059. These findings strongly suggest that the regulation of transmembrane signaling by HCV E2 protein via its receptor(s) on host cells might contribute to the development of HCV-related diseases.展开更多
基金Project supported by the National Natural Science Foundation of China, Shanghai Joint Laboratory of Life Science, Shanghai Institute of Cell Biology, and Director's Foundations of Chinese Academy of Sciences and Shanghai Institute of Cell Biology.
文摘Little is known about the mechanism and signal transduction by LPS-mediated immunomodulation of murine peritoneal macrophages. It is found that the signal molecules of the down-stream of Ras, Raf-1, MAPK p44, and MAPK p42 are phosphorylated, and cPLA2 is activated with a significant increase of the release of [ H3 ] AA by macrophages in response to LPS and PMA. Compared with the very recent finding that LPS and PMA trigger the activation and translocation of PKC-α and PKC-ε, these findings suggest that there is a connection between PKC signaling pathway and the Raf-1/MAPK pathway and that the activation of these main signaling events may be closely related to the secretion of IL-12 during LPS-induced modulation of macrophages.
基金supported by the National Natural Science Foundation of China(Grant No.30170514)the State 863 High Technology R&D Project of China(No.2002AA214161).
文摘Since cell signal transduction plays an important role in disclosing the nature of human diseases, the pathogenesis of viruses may result from the disturbance of intracellular signal cascades caused by viral proteins. Hepatitis C virus (HCV) is a main causative agent of severe human liver disorders worldwide. So far, the mechanisms of HCV pathogenicity remain unclear. Envelope protein 2 (E2) of HCV is thought to be responsible for initiating virus attachment to host cells, which is a prerequisite of HCV infection. We assume that some early events of HCV pathogenic effects may result from the interaction of HCV E2 protein with its cellular receptor (human CD81), which could regulate cell proliferation and differentiation. To test this hypothesis, the effects of HCV E2 protein on MAPK/ERK pathway in Molt-4 and U937 cells with or without human CD81 expression were investigated. The results showed that HCV E2 protein could specifically activate the MAPK/ERK pathway, and such activation was inhibited by monoclonal antibodies against CD81 or HCV E2, serum antibodies from HCV infected patients, and upstream MEK1 inhibitor PD98059. Moreover, HCV E2-driven MAPK/ERK or downstream transcription factor Elk-1 activation was completely blocked in the presence of PD98059. These findings strongly suggest that the regulation of transmembrane signaling by HCV E2 protein via its receptor(s) on host cells might contribute to the development of HCV-related diseases.
