IFN c F Is dependent Ngig BMDM. Macrophage responses to IFN c discussions are mediated to a large Ma E of the JAK STAT pathway.6, 7 Nevertheless, the fact that IFN c regulates the expression of many genes in cells without STAT1, and activates the PI3K and ERK1 SB-715992 Ispinesib / 2 in cells lacking either JAK1 or JAK2, 7.10 is compatible with the notion that other signaling pathways contribute to the modulation of cellular Ren responses by IFN c. Were 10, 35 The involvement of PKC isozymes in the regulation of IFN responses by the alternating current induced in various systems.14 18.20 have been described in macrophages, are previously shown that PKC translocation into the nucleus in response to IFN c, and that the activity of PKC-t c regulates IFN-induced MHC II expression by modulating the F ability of IRF 1, transactivate the CIITA promoter IV.
20 In this study, we found that two PI3K and p38 MAPK be involved in the activation of PKC in macrophages induced by IFN c, and we further characterized the r these kinases in the regulation of IFN-induced responses in macrophages c. The activation of Baicalein PI3K by both Type I and Type II IFN in several cell-types.8, 10,14,17,36,37 A key consequence of activation of PI3K has been reported is the phosphorylation of STAT1 at serine 727, shown , that was mediated by PKC d in human acute Promyelozytenleuk mie cells 14 or e PKC in rat mesanglial cells.17 In BMDM, we found that IFN-induced STAT1 serine 727 phosphorylation of c requires PKC but is independent Ngig of PI3K. This is consistent with the observation that PI3K had no effect on the phosphorylation of PKC A.
The finding that PI3K was required for IFN c stimulates the nucleic Re translocation of PKC A schl Gt the existence of at least two steps in the regulation of PKC activation of IFN c stimulated BMDM. Therefore, the first phase of the tire 30 by PKC regulates a yet unidentified way, w During step targeting PI3K. Although both type I and type II IFN activate p38 MAPK, the R This kinase in the modulation of the IFN response remains poorly understood. W While p38 MAPK is required for STAT1 gene expression entered Born in response to IFN and IFN-b, does it matter In the regulation of expression of chemokines important in IFN stimulated macrophages.11 andcytokines c, 19 In previous reports, 19.38, 39 we found that in BMDM, p38 MAPK is responsible for IFN-induced phosphorylation of c-STAT1 at serine 727 or required for expression of IRF-1, CIITA and MHC-II.
These events are clearly from the IFN-induced c-chemokine and cytokine expression. As p38 MAPK in the nucleon Ren translocation of PKC has been involved, it is tempting to speculate that PKC may be involved in regulation of chemokine and cytokine expression. As p38 MAPK was in the initial phase of PKC activation by IFN c, where the mechanism by which p38 MAPK module of the nucleic Ren translocation of PKC remains to be identified involved. We previously reported that PKC activity t c regulates IFN-induced MHC II expression by modulating the F Ability of IRF 1 to transactivate the CIITA promoter stimulates IV.20 In line with these previous results, IFN type IV CIITA and c MHC II expression was strongly inhibited by Go 6976 ¨. Our data also show that, w While the PI3K and p38 M