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The Journal of Immunology, 2007, 178: 6307-6315.
Copyright © 2007 by The American Association of Immunologists, Inc.

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Lipopolysaccharide Up-Regulates MHC Class II Expression on Dendritic Cells through an AP-1 Enhancer without Affecting the Levels of CIITA1

Cristina Casals, Marta Barrachina, Maria Serra, Jorge Lloberas and Antonio Celada2

Macrophage Biology Group, Institute for Research in Biomedicine, University of Barcelona, Barcelona, Spain

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.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

1 This work was supported by Ministerio de Ciencia y Tecnología Grant BFU2004-05725/BMC (to A.C.).

2 Address correspondence and reprint requests to Dr. Antonio Celada, Macrophage Biology Group, Institute for Research in Biomedicine, University of Barcelona, Barcelona Science Park, Josep Samitier 1-5, E-08028 Barcelona, Spain. E-mail address: acelada{at}ub.edu

3 Abbreviations used in this paper: MHC II, MHC class II; RFX, regulatory factor X; DRB, dichlorobenzimidazole riboside; GAS, IFN-{gamma} activation site.




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C. Sebastian, M. Serra, A. Yeramian, N. Serrat, J. Lloberas, and A. Celada
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[Abstract] [Full Text] [PDF]




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