Role of the interferon-inducible IFI16 gene in the induction of ICAM-1 by TNF-alpha

The Interferon-inducible gene IFI16, a member of the HIN200 family, is activated by oxidative stress and cell density, in addition to Interferons, and it is implicated in the regulation of endothelial cell proliferation and vessel formation in vitro. We have previously shown that IFI16 is required for proinflammatory gene stimulation by IFN-γ through the NF-κB complex. To examine whether IFI16 induction might be extended to other proinflammatory cytokines such as tumor necrosis factor (TNF)-α, we used the strategy of the RNA interference to knock down IFI16 expression, and analyze the capability of TNF-α to stimulate intercellular adhesion molecule-1 (ICAM-1 or CD54) expression in the absence of functional IFI16. Our studies demonstrate that IFI16 mediates ICAM-1 stimulation by TNF-α through the NF-κB pathway, thus reinforcing the role of the IFI16 molecule in the inflammation process.