Guo Xinkun, Zhu Zhaoqin, Zhang Wanju, Meng Xiaoxiao, Zhu Yong, Han Peng, Zhou Xiaohui, Hu Yunwen, Wang Ruilan
Department of Critical Care Medicine, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200080, China.
Department of Pathogen Diagnosis and Biosafety, Shanghai Public Health Clinical Center, Key Laboratory of Medical Molecular Virology, Ministry of Education and Health, Shanghai Medical College, Fudan University, Shanghai 201508, China.
Emerg Microbes Infect. 2017 May 24;6(5):e39. doi: 10.1038/emi.2017.21.
Infection with the influenza A (H1N1) virus is a major challenge for public health because it can cause severe morbidity and even mortality in humans. The over-secretion of inflammatory cytokines (cytokine storm) is considered to be a key contributor to the severe pneumonia caused by H1N1 infection. It has been reported that hypoxia-inducible factor 1-alpha (HIF-1α) is associated with the production of proinflammatory molecules, but whether HIF-1α participates in the acute inflammatory responses against H1N1 infection is still unclear. To investigate the role of HIF-1α in H1N1 infection, the expression and nuclear translocation of HIF-1α in A549 and THP-1 cell lines infected with H1N1 virus were observed. The results showed that without altering the intracellular mRNA or protein expression of HIF-1α, H1N1 infection only induced nuclear translocation of HIF-1α under normal oxygen concentrations. The use of 2-methoxyestradiol (2ME2), a HIF-1α inhibitor that blocks HIF-1α nuclear accumulation, in H1N1-infected cells decreased the mRNA and protein expression of tumor necrosis factor-alpha (TNF-α) and interleukin (IL)-6 and increased the levels of IL-10. In contrast, H1N1-infected cells under hypoxic conditions had increased HIF-1α nuclear accumulation, increased expression of TNF-α and IL-6 and decreased levels of IL-10. In conclusion, our data implied that in vitro H1N1 infection induced nuclear translocation of HIF-1α without altering the expression of HIF-1α, which may promote the secretion of proinflammatory cytokines during H1N1 infection.
甲型H1N1流感病毒感染是公共卫生面临的一项重大挑战，因为它可导致人类出现严重发病甚至死亡。炎性细胞因子过度分泌（细胞因子风暴）被认为是H1N1感染所致严重肺炎的关键促成因素。据报道，缺氧诱导因子1α（HIF-1α）与促炎分子的产生有关，但HIF-1α是否参与针对H1N1感染的急性炎症反应仍不清楚。为了研究HIF-1α在H1N1感染中的作用，观察了H1N1病毒感染的A549和THP-1细胞系中HIF-1α的表达及核转位情况。结果显示，在不改变HIF-1α细胞内mRNA或蛋白表达的情况下，H1N1感染仅在正常氧浓度下诱导HIF-1α核转位。在H1N1感染的细胞中使用2-甲氧基雌二醇（2ME2），一种可阻断HIF-1α核蓄积的HIF-1α抑制剂，可降低肿瘤坏死因子-α（TNF-α）和白细胞介素（IL）-6的mRNA和蛋白表达，并提高IL-10水平。相反，缺氧条件下H1N1感染的细胞HIF-1α核蓄积增加，TNF-α和IL-6表达增加，IL-10水平降低。总之，我们的数据表明，体外H1N1感染诱导HIF-1α核转位但不改变HIF-1α的表达，这可能在H1N1感染期间促进促炎细胞因子的分泌。
