“炎症风暴”及凋亡是造成严重流感肺炎重要因素，应用药物阻断关键机制进行防治一直是公共卫生亟待需求。我们前期发现，IFN-β预刺激增加ISGF3转录而加剧流感介导炎症和凋亡。连苯三酚抑制RIG-I信号阻断IFN-β预刺激增加ISGF3转录活性。尚无阻断IFN-β预刺激治疗流感肺炎报道。据此我们提出假说：连苯三酚抑制RIG-I信号而阻断ISGF3转录，治疗IFN-β致敏加剧流感介导炎症和凋亡。本课题拟从分子、细胞及体内水平等多层次明确IFN-β预刺激加剧流感介导炎症和凋亡作用；探讨RIG-I信号调控IFN-β预刺激加剧ISGF3转录机制；确定连苯三酚对IFN-β预刺激加剧流感炎症和凋亡作用；阐明连苯三酚抑制RIG-I信号削弱了IFN-β预刺激增加ISGF3转录而抑制放大流感炎症和凋亡机制。本研究将从连苯三酚抑制IFN-β致敏加剧炎症及凋亡这个新观点，为严重流感肺炎防治提供新思路及新型候选药物。

“Cytokine storm” and apoptosis are critical factors for severe influenza pneumonia, and blockade of the key mechanism involved in severe influenza pneumonia by novel agents has been as an urgent need for public health in the prophylaxis and therapeutic of severe influenza pneumonia. We previously found that IFN-β prestimulation increased the transcriptional activity of ISGF3, and thus exacerbated influenza virus-mediated inflammation and apoptosis. Inhibition of RIG-I signaling by pyrogallol suppressed the IFN-β prestimulation-trigged amplification of ISGF3 transcriptional activity. Blockade of IFN-β prestimulation in the treatment of influenza-associated pneumonia has not been reported in the previous studies. Therefore, we hypothesized that inhibition of RIG-I signaling by pyrogallol leads to abrogate the transcriptional activity of ISGF3, which resulted in suppression of exacerbated influenza virus-mediated inflammation and apoptosis in IFN-β-pretreated cells. The purpose of this project would be carried out to at molecular, cellular and in vivo levels to clarify the role of IFN-β pretreatment in amplification of influenza-mediated inflammation and apoptosis and investigate the mechanism of RIG-I signaling enhanced the transcriptional activity of ISGF3. Meanwhile, we set out to determine the effect of pyrogallol on IFN-β prestimulation-exacerbated influenza virus-mediated inflammation and apoptosis and elucidate the molecular mechanism of reduction of IFN-β pretreatment-amplified influenza-mediated inflammation and apoptosis by RIG-I signaling inhibition. This project will focus on inhibition of IFN-β pretreated-mediated amplification of influenza-mediated inflammation and apoptosis by pyrogallol treatment, which would provide new perspective and novel candidate drug for the prevention and treatment of severe influenza pneumonia.