Human Gene Set: GSE10463_CD40L_AND_VA347_VS_CD40L_IN_DC_DN
Standard name
GSE10463_CD40L_AND_VA347_VS_CD40L_IN_DC_DN
Systematic name
M3099
Brief description
Genes down-regulated in comparison of dendritic cells activated in the absense of VAF347 [PubChem=10172275] versus those activated in the presence of VAF347 [PubChem=10172275].
Full description or abstract
VAF347 is a low molecular weight compound which inhibits allergic lung inflammation in vivo. This effect is likely due to a block of dendritic cell (DC) function to generate pro-inflammatory T-helper (Th) cells since VAF347 inhibits IL-6, CD86 and HLA-DR expression by human monocyte derived DC, three relevant molecules for Th-cell generation. Here we demonstrate that VAF347 interacts with the aryl hydrocarbon receptor (AhR) protein resulting in activation of the AhR signaling pathway. Functional AhR is responsible for the biological activity of VAF347 since, i) other AhR agonists display an identical activity profile in vitro, ii) gene silencing of wild type AhR expression or forced over-expression of a trans-dominant negative AhR ablates VAF347 activity to inhibit cytokine induced IL-6 expression in a human monocytic cell line and iii) AhR deficient mice are resistant to the compound?s ability to block allergic lung inflammation in vivo. These data identify the AhR protein as key molecular target of VAF347 and its essential role for mediating the anti-inflammatory effects of the compound in vitro and in vivo.
