Sponza Simone, De Andrea Marco, Mondini Michele, Gugliesi Francesca, Gariglio Marisa, Landolfo Santo
Department of Public Health and Microbiology, Medical School of Turin, Laboratory of Viral Pathogenesis, Turin, Italy.
Cell Immunol. 2009;257(1-2):55-60. doi: 10.1016/j.cellimm.2009.02.007. Epub 2009 Mar 31.
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-gamma through the NF-kappaB complex. To examine whether IFI16 induction might be extended to other proinflammatory cytokines such as tumor necrosis factor (TNF)-alpha, we used the strategy of the RNA interference to knock down IFI16 expression, and analyze the capability of TNF-alpha 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-alpha through the NF-kappaB pathway, thus reinforcing the role of the IFI16 molecule in the inflammation process.
干扰素诱导基因IFI16是HIN200家族的成员之一，除了受干扰素激活外，还可被氧化应激和细胞密度激活，并且在体外参与内皮细胞增殖和血管形成的调节。我们之前已经表明，IFI16是IFN-γ通过NF-κB复合体刺激促炎基因所必需的。为了研究IFI16的诱导是否可能扩展到其他促炎细胞因子，如肿瘤坏死因子（TNF）-α，我们采用RNA干扰策略敲低IFI16的表达，并分析在缺乏功能性IFI16的情况下TNF-α刺激细胞间黏附分子-1（ICAM-1或CD54）表达的能力。我们的研究表明，IFI16通过NF-κB途径介导TNF-α对ICAM-1的刺激，从而加强了IFI16分子在炎症过程中的作用。
