Lipopolysaccharide up-regulates MHC class II expression on dendritic cells through an AP-1 enhancer without affecting the levels of CIITA.
The expression of MHC class II genes is strictly tissue specific. In a limited number of cells, the expression of these genes is inducible by cytokines and only in dendritic and B cells is expression constitutive. LPS blocks the cytokine-dependent induction of these genes, but enhances their expression in dendritic and the B cell line A20. We have observed that LPS increased surface expression by raising I-A protein and mRNA levels. LPS does not enhance the expression of the transactivator CIITA. In transient transfection experiments, LPS induced the expression of the I-Abeta promoter, which contains an AP-1 box located between 1722 and 1729 bp upstream of the transcriptional start site. Mutation of this box abrogated the effect of LPS. The AP-1 box still responded to LPS when we moved it to -611 bp or even when it was in the opposite direction. LPS induced a complex that bound to the AP-1 box. However, in dendritic cells, the complex comprised c-jun and c-fos while in A20 cells only c-jun. This was confirmed by chromatin immune precipitation assays and the distinct induction of c-jun and c-fos mRNAs. Therefore, our results indicate that LPS exerts a novel regulatory mechanism in the control of MHC class II gene expression.
Casals
Cristina
C
Macrophage Biology Group, Institute for Research in Biomedicine, University of Barcelona, Barcelona, Spain.
Barrachina
Marta
M
Serra
Maria
M
Lloberas
Jorge
J
Celada
Antonio
A
D000818:Animals; D002460:Cell Line; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism*; D004742:Enhancer Elements, Genetic / Q000502:physiology*; D015972:Gene Expression Regulation, Neoplastic / Q000276:immunology; D005802:Genes, MHC Class II / Q000235:genetics* / Q000276:immunology; D008070:Lipopolysaccharides / Q000494:pharmacology*; D051379:Mice; D009687:Nuclear Proteins / Q000378:metabolism*; D015534:Trans-Activators / Q000378:metabolism*; D018808:Transcription Factor AP-1 / Q000502:physiology*; D015854:Up-Regulation / Q000276:immunology*
D008070:Lipopolysaccharides; C083728:MHC class II transactivator protein; D009687:Nuclear Proteins; D015534:Trans-Activators; D018808:Transcription Factor AP-1