Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2006-6-20
pubmed:abstractText
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-gamma-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-gamma-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-gamma induction of CIITA. Moreover, the induction of CIITA by IFN-gamma 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.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
0022-1767
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
177
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
70-6
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:16785500-Adaptor Proteins, Signal Transducing, pubmed-meshheading:16785500-Animals, pubmed-meshheading:16785500-Bone Marrow Cells, pubmed-meshheading:16785500-Cell Line, pubmed-meshheading:16785500-Cells, Cultured, pubmed-meshheading:16785500-Dendritic Cells, pubmed-meshheading:16785500-Down-Regulation, pubmed-meshheading:16785500-Extracellular Signal-Regulated MAP Kinases, pubmed-meshheading:16785500-Lipopolysaccharides, pubmed-meshheading:16785500-MAP Kinase Signaling System, pubmed-meshheading:16785500-Macrophages, pubmed-meshheading:16785500-Mice, pubmed-meshheading:16785500-Mice, Inbred C57BL, pubmed-meshheading:16785500-Mice, Knockout, pubmed-meshheading:16785500-Myeloid Differentiation Factor 88, pubmed-meshheading:16785500-Nuclear Proteins, pubmed-meshheading:16785500-Trans-Activators, pubmed-meshheading:16785500-p38 Mitogen-Activated Protein Kinases
pubmed:year
2006
pubmed:articleTitle
ERK and p38 MAPK signaling pathways negatively regulate CIITA gene expression in dendritic cells and macrophages.
pubmed:affiliation
Department of Microbiology and Immunology, Walther Oncology Center, Indiana University School of Medicine, 950 West Walnut Street R2-302, Indianapolis, IN 46202, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural