کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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2515086 | 1118500 | 2006 | 8 صفحه PDF | دانلود رایگان |
Type I IFN (IFN-α/β) have important biological functions ranging from immune cell development and activation, to tumor cell killing and most importantly inhibition of virus replication. Following viral infection or activation of Toll-like receptors (TLRs) via distinct ligands, IFN-α/β are produced. Two members of the interferon regulatory factor (IRF) family – IRF-3 and IRF-7 – are the major modulators of IFN gene expression. Activation of IRF-3 and IRF-7 by TBK1/IKKɛ mediated phosphorylation promotes IFN gene expression and potentiates the production of IFN responsive genes important to the development of an effective antiviral immune response. IFN treatment can augment anti-tumor properties and they are potentially key players in cancer therapy. For example, adoptive transfer of IFN-γ-activated macrophages can mediate tumor cell killing via direct cell–cell contact, as well as release of soluble cytotoxic pro-inflammatory molecules. A recent study investigated whether IRF-3 and IRF-7 could mediate the acquisition of new anti-tumor effector functions in macrophages. Adenovirus mediated transduction of the active form of IRF-7 into primary macrophages resulted in the production of type I IFN, upregulation of target genes including TRAIL and increased tumoricidal activity of macrophages; in contrast, the active form of IRF-3 led to induction of cell death. These studies indicate that IRF-7 transduced macrophages may be an attractive candidate for in vivo adoptive therapy of cancer.
Journal: Biochemical Pharmacology - Volume 72, Issue 11, 30 November 2006, Pages 1469–1476