Lipopolysaccharide up-regulates MHC class II expression on dendritic cells through an AP-1 enhancer without affecting the levels of C11TA
Lipopolysaccharide up-regulates MHC class II expression on dendritic cells through an AP-1 enhancer without affecting the levels of C11TA
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DOI：
10.4049/jimmunol.178.10.6307
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发表时间：
2007-05-15
影响因子：
4.4
通讯作者：
Celada, Antonio
中科院分区：
文献类型：
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作者：
Casals, Cristina;Barrachina, Marta;Celada, Antonio
MHC H类基因的表达具有严格的组织特异性。在有限数量的细胞中，这些基因的表达可被细胞因子诱导，并且仅在树突细胞和B细胞中是表达组成型的。LPS阻断了这些基因的精氨酸依赖性诱导，但增强了它们在树突状细胞和B细胞系A20中的表达。我们已经观察到LPS通过提高I-A β蛋白和mRNA水平来增加表面表达。LPS不增强反式激活因子CUTA的表达。在瞬时转染实验中，LPS诱导I-A β启动子的表达，该启动子包含位于转录起始位点上游1722和1729 bp之间的AP-1盒。该框的突变消除了LPS的作用。当我们将AP-1框移动到-611 bp时，甚至当它在相反方向时，AP-1框仍然对LPS有反应。LPS诱导了与AP-1盒结合的复合物。而在树突状细胞中，c-jun和c-fos的复合体由c-jun和c-fos组成，而在A20细胞中，c-jun和c-fos的mRNA的表达明显增加，而在树突状细胞中，c-jun和c-fos的mRNA的表达明显增加，而在A20细胞中，c-jun和c-fos的mRNA的表达明显增加。因此，我们的研究结果表明，LPS发挥一种新的调节机制，在控制MHC H类基因的表达。
The expression of MHC class H 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 beta protein and mRNA levels. LPS does not enhance the expression of the transactivator CUTA. In transient transfection experiments, LPS induced the expression of the I-A beta 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 H gene expression.