| First Author | Valledor AF | Year | 2008 |
| Journal | J Immunol | Volume | 180 |
| Issue | 7 | Pages | 4523-9 |
| PubMed ID | 18354174 | Mgi Jnum | J:132992 |
| Mgi Id | MGI:3777501 | Doi | 10.4049/jimmunol.180.7.4523 |
| Citation | Valledor AF, et al. (2008) Selective Roles of MAPKs during the Macrophage Response to IFN-{gamma}. J Immunol 180(7):4523-9 |
| abstractText | Macrophages perform essential functions in the infection and resolution of inflammation. IFN-gamma is the main endogenous macrophage Th1 type activator. The classical IFN-gamma signaling pathway involves activation of Stat-1. However, IFN-gamma has also the capability to activate members of the MAPK family. In primary bone marrow-derived macrophages, we have observed strong activation of p38 at early time points of IFN-gamma stimulation, whereas weak activation of ERK-1/2 and JNK-1 was detected at a more delayed stage. In parallel, IFN-gamma exerted repressive effects on the expression of a number of MAPK phosphatases. By using selective inhibitors and knockout models, we have explored the contributions of MAPK activation to the macrophage response to IFN-gamma. Our findings indicate that these kinases regulate IFN-gamma-mediated gene expression in a rather selective way: p38 participates mainly in the regulation of the expression of genes required for the innate immune response, including chemokines such as CCL5, CXCL9, and CXCL10; cytokines such as TNF-alpha; and inducible NO synthase, whereas JNK-1 acts on genes involved in Ag presentation, including CIITA and genes encoding MHC class II molecules. Modest effects were observed for ERK-1/2 in these studies. Interestingly, some of the MAPK-dependent changes in gene expression observed in these studies are based on posttranscriptional regulation of mRNA stability. |
