Figure 3. Schematic overview of the mechanism underlying TNF-α and IFN-γ synergism.
IFN-γ and TNF-α synergistically modulate the expression of different inflammatory genes such ICAM-1, RANTES, IL-8 and CD38. Their cooperativity may be explained at the receptor level by the IFNγ-induced up-regulation of TNF-α receptors or vice-versa. Alternatively, both cytokines may collaborate at the gene level by increasing promoter activation through a synergistic interaction between transcription factors activated by IFN-γ (STATs, IRF-1) and TNF-α (NF-κB). Another mechanism underlying such cooperation could be the induction of defined genes by TNF-α via activation of the autocrine action of IFN-β.