Role of PKCδ in IFN-γ-inducible CIITA gene expression

The class II transactivator (CIITA) is a key regulatory factor for MHC class II expression. Here, we demonstrate that PKC delta plays an important role in regulating IFN-gamma-inducible CIITA gene expression in macrophages. Inhibition of PKC delta by either a PKC delta inhibitor or a dominant negative (DN) mutant form of PKC delta led to down-regulation of CIITA expression. The decrease in CIITA expression by PKC delta inhibition was in part due to the reduced recruitment of serine 727-phosphorylated Stat1 and histone acetyltransferases to the CIITA promoter. As a result, IFN-gamma induced histone acetylation at the CIITA promoter is also compromised. However, inhibition of PKC delta did not affect IRF-1 expression or IRF-1 binding to the CIITA promoter. Therefore, we report, for the first time, that PKC delta is an essential signaling molecule to achieve the maximal expression of CIITA in response to IFN-gamma in macrophages. In addition, although IRF1- is a key transcription factor to activate the IFN-gamma inducible CIITA promoter, the effect of PKC delta on CIITA expression is mediated primarily by serine phosphorylation of Stat 1. (c) 2007 Elsevier Ltd. All rights reserved.