CCAAT/enhancer-binding protein beta and delta binding to CIITA promoters is associated with the inhibition of CIITA expression in response to Mycobacterium tuberculosis 19-kDa lipoprotein.
TLR2 signaling by Mycobacterium tuberculosis 19-kDa lipoprotein (LpqH) inhibits IFN-gamma-induced expression of CIITA by macrophages. Microarray analysis, quantitative RT-PCR, and Western blots showed that LpqH induced C/EBPbeta and C/EBPdelta in kinetic correlation with inhibition of CIITA expression. Of the C/EBPbeta isoforms, liver inhibitory protein (LIP) was notably induced and liver-activating protein was increased by LpqH. Putative C/EBP binding sites were identified in CIITA promoters I and IV (pI and pIV). LpqH induced binding of C/EBPbeta (LIP and liver-activating protein) to biotinylated oligodeoxynucleotide containing the pI or pIV binding sites, and chromatin immunoprecipitation showed that LpqH induced binding of C/EBPbeta and C/EBPdelta to endogenous CIITA pI and pIV. Constitutive expression of C/EBPbeta LIP inhibited IFN-gamma-induced CIITA expression in transfected cells. In summary, LpqH induced expression of C/EBPbeta and C/EBPdelta, and their binding to CIITA pI and pIV, in correlation with inhibition of IFN-gamma-induced expression of CIITA in macrophages, suggesting a role for C/EBP as a novel regulator of CIITA expression.
Pennini
Meghan E
ME
Department of Pathology, Case Western Reserve University, Cleveland, OH 44106, USA.
Liu
Yi
Y
Yang
Jianqi
J
Croniger
Colleen M
CM
Boom
W Henry
WH
Harding
Clifford V
CV
D000818:Animals; D001426:Bacterial Proteins / Q000276:immunology / Q000494:pharmacology*; D015153:Blotting, Western; D022782:CCAAT-Enhancer-Binding Protein-beta / Q000276:immunology / Q000378:metabolism*; D051743:CCAAT-Enhancer-Binding Protein-delta / Q000276:immunology / Q000378:metabolism*; D002460:Cell Line; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects* / Q000276:immunology; D008264:Macrophages / Q000276:immunology / Q000378:metabolism; D051379:Mice; D009169:Mycobacterium tuberculosis / Q000276:immunology; D009687:Nuclear Proteins / Q000096:biosynthesis* / Q000276:immunology; D020411:Oligonucleotide Array Sequence Analysis; D020218:Response Elements / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015534:Trans-Activators / Q000096:biosynthesis* / Q000276:immunology
D001426:Bacterial Proteins; D022782:CCAAT-Enhancer-Binding Protein-beta; C510627:LpqW protein, Mycobacterium tuberculosis; C083728:MHC class II transactivator protein; D009687:Nuclear Proteins; D015534:Trans-Activators; D051743:CCAAT-Enhancer-Binding Protein-delta