Molecular mechanism of acute pancreatitis provoked by double-stranded RNA

总的来说，这项研究的结果提供了证据，转录因子IRF-2是所需的胰腺腺泡细胞的发展和/或成熟，并在保护对dsRNA诱导的细胞凋亡。后者意味着，在IRF-2表达的情况下，胰腺腺泡细胞变得对病毒感染以及poly（I）：polyc诱导的凋亡敏感。先前的研究表明，IRF-2的抗凋亡作用是通过调节IFN诱导的促凋亡基因的表达来介导的。然而，在缺乏IRF-2的胰腺腺泡细胞中，poly（I）：polyc对这些基因表达的诱导没有显著改变，这表明除了IFN诱导的促凋亡基因之外的基因也参与其中。虽然我们目前还不知道IRF-2表达在胰腺中是如何生理性下调的，但有趣的是推测 关于我们 一些特发性胰腺炎病例可能是在IRF-2浓度异常低的情况下由潜伏性病毒感染引起的。有趣的是，人类免疫缺陷病毒（HIV）感染通常与胰腺炎相关，而疱疹病毒8/卡波西肉瘤相关疱疹病毒（HHV-8/KSHV）是HIV相关卡波西肉瘤中的偶然因子，在开放阅读框K9中编码病毒IRF（vIRF）-2。体外结合试验证实了重组vIRF-2与细胞ERF-2、RelA或p300之间的关联，并且vIRF-2对IRF-2具有显性负活性。由于KSHV已被建议感染胰腺，因此，我们假设，这是可能的，艾滋病患者感染这种病毒表现出减少IRF-2表达的胰腺，因此，易于发病诱导胰腺炎后，机会性病毒感染。在我们的小鼠胰腺炎模型中检测来源于KSHV的vIRF-2的可能参与的研究正在进行中。少

Collectively, the results of this study provide evidence that the transcription factor IRF-2 is required by pancreatic acinar cells for both their development and/or maturation, and in protection against dsRNA-induced apoptosis. The latter implies that in the absence of IRF-2 expression, pancreatic acinar cells become susceptible to apoptosis induced by virus infections as well as by poly(I):polyc. Previous studies have shown that the anti-apoptotic effect of IRF-2 is mediated through the regulation of expression of IFN-inducible pro-apoptotic genes. However, the induction of the expression of these genes by poly(I):polyc was not significantly altered in pancreatic acinar cells lacking IRF-2, suggesting that genes other than the IFN-inducible pro-apoptotic genes examined here are involved.Clinically, 10% of pancreatitis is diagnosed as idiopathic. Although we do not know at present how IRF-2-expression may be physiologically downregulated in the pancreas, it is interesting to speculate … More that some cases of idiopathic pancreatitis might be caused by latent viral infections in the presence of abnormally low concentrations of IRF-2. Intriguingly, human immunodeficiency virus (HIV) infection has often been associated with pancreatitis, and herpes virus 8/Kaposi sarcoma-associated herpes virus (HHV-8/KSHV), the casual factor in HIV-associated Kaposi sarcoma, encodes viral IRF (vIRF)-2 in open reading frame K9. An in vitro binding assay confirmed the association between recombinant vIRF-2 and cellular ERF-2, RelA, or p300, and vIRF-2 is proposed to have a dominant negative activity on IRF-2. Because KSHV has been suggested to infect the pancreas, we therefore hypothesize that it is possible that AIDS patients infected with this virus exhibit decreased IRF-2 expression in the pancreas and are therefore prone to apoptosis-induced pancreatitis after opportunistic virus infections. Study to examine in our murine model pancreatits the possible involvement of vIRF-2 derived from KSHV is underway. Less