TGFbeta-dependent gene expression profile during maturation of dendritic cells.
Primary immune response to pathogens involves the maturation of antigen-presenting dendritic cells (DC). Bacterial lipopolysacharride (LPS) is a potent inducer of DC maturation, whereas the transforming growth factor beta (TGFbeta) attenuates much of this process. Here, we analyzed the global gene expression pattern in LPS-treated bone marrow derived DC during inhibition of their maturation process by TGFbeta. Exposure of DC to LPS induces a pronounced cell response, manifested in altered expression of a large number of genes. Interestingly, TGFbeta did not affect most of the LPS responding genes. Nevertheless, analysis identified a subset of genes that did respond to TGFbeta, among them the two inflammatory cytokines interleukin (IL)-12 and IL-18. Expression of IL-12, the major proinflammatory cytokine secreted by mature DC, was downregulated by TGFbeta, whereas the expression level of the proinflammatory cytokine IL-18, known to potentiate the IL-12 effect, was upregulated. Expression of the peroxisome proliferator-activated receptor gamma (PPARgamma) increased in response to TGFbeta, concomitantly with reduced expression of chemokine receptor 7 (CCR7). This finding supports the possibility that TGFbeta-dependent inhibition of CCR7 expression in DC is mediated by PPARgamma.
Fainaru
O
O
Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel.
Shay
T
T
Hantisteanu
S
S
Goldenberg
D
D
Domany
E
E
Groner
Y
Y
D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism*; D015870:Gene Expression / Q000187:drug effects*; D020869:Gene Expression Profiling; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D066298:In Vitro Techniques; D018664:Interleukin-12 / Q000235:genetics; D020382:Interleukin-18 / Q000235:genetics; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D020411:Oligonucleotide Array Sequence Analysis; D011994:Recombinant Proteins / Q000494:pharmacology; D016212:Transforming Growth Factor beta / Q000494:pharmacology*
D020382:Interleukin-18; D008070:Lipopolysaccharides; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; D018664:Interleukin-12; D016178:Granulocyte-Macrophage Colony-Stimulating Factor