ERK and p38 MAPK Signaling Pathways Negatively Regulate CIITA Gene Expression in Dendritic Cells and Macrophages
| Autor: | Myung Ja Kwon, Yongxue Yao, Soon Choel Hong, Yusen Liu, Ranyia Matta, Qi Xu, Cheong Hee Chang |
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| Rok vydání: | 2006 |
| Předmět: |
Lipopolysaccharides
MAPK/ERK pathway MAP Kinase Signaling System p38 mitogen-activated protein kinases Immunology CIITA Gene Down-Regulation Bone Marrow Cells chemical and pharmacologic phenomena p38 Mitogen-Activated Protein Kinases Cell Line Mice Downregulation and upregulation MHC class I CIITA Animals Immunology and Allergy Extracellular Signal-Regulated MAP Kinases Cells Cultured Adaptor Proteins Signal Transducing Mice Knockout MHC class II biology Chemistry Macrophages Nuclear Proteins Dendritic Cells Mice Inbred C57BL Cell culture Myeloid Differentiation Factor 88 Trans-Activators biology.protein Cancer research |
| Zdroj: | The Journal of Immunology. 177:70-76 |
| ISSN: | 1550-6606 0022-1767 |
| DOI: | 10.4049/jimmunol.177.1.70 |
| Popis: | The CIITA is a master regulator for MHC class II expression, but the signaling events that control CIITA expression remain poorly understood. In this study, we report that both constitutive and IFN-γ-inducible expression of CIITA in mouse bone marrow-derived dendritic cells (DC) and macrophages, respectively, are regulated by MAPK signals. In DC, the inhibitory effect of LPS on CIITA expression was prevented by MyD88 deficiency or pharmacological MAPK inhibitors specific for MEK (U0126) and p38 (SB203580), but not JNK (SP600125). In macrophages, LPS inhibited IFN-γ-inducible CIITA and MHC class II expression without affecting expression of IFN regulatory factor-1 and MHC class I. Blocking ERK and p38 by MAPK inhibitors not only rescued LPS-mediated inhibition, but also augmented IFN-γ induction of CIITA. Moreover, the induction of CIITA by IFN-γ was enhanced by overexpressing MAPK phosphatase-1 that inactivates MAPK. Conversely, CIITA expression was attenuated in the absence of MAPK phosphatase-1. The down-regulation of CIITA gene expression by ERK and p38 was at least partly due to decreased histone acetylation of the CIITA promoter. Our study indicates that both MAPK and phosphatase play an important role for CIITA regulation in DC and macrophages. |
| Databáze: | OpenAIRE |
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