Caspase-8 激活调控肠道病毒 D68 感染诱发的炎症反应和细胞死亡

IF 3.5 Q1 PUBLIC, ENVIRONMENTAL & OCCUPATIONAL HEALTH
Yuanyuan Zhou , Chongtao Zhang , Yuhan Zhang , Fei Li , Jun Shen
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引用次数: 0

摘要

肠道病毒 D68(EV-D68)感染会导致儿童严重的急性呼吸道感染和严重的神经系统并发症,如急性弛缓性脊髓炎(AFM)。然而,尽管 EV-D68 有可能大流行,但目前临床上还没有有效的药物或疫苗。此外,EV-D68 感染诱导的炎症反应和细胞死亡尚未完全明了。在这项研究中,我们证实了在 EV-D68 感染的人横纹肌肉瘤(RD)细胞中,几种炎症细胞因子以依赖感染倍数(MOI)的方式上调。定量逆转录酶聚合酶链反应(qRT-PCR)证实,EV-D68感染后,肿瘤坏死因子-α(TNF-α)、白细胞介素6(IL-6)、C-C马达趋化因子配体-5(CCL-5)和CXC马达趋化因子配体-5(CXCL-5)的mRNA水平高度上调。Caspase-8抑制剂Z-IETD-FMK抑制了Caspase-8介导的IL-1β加工和成熟。EV-D68感染激活了caspase-8,从而介导了IL-1β的成熟和分泌。此外,EV-D68 还激活了与细胞死亡相关的蛋白,如 caspase-3、多聚(ADP-核糖)聚合酶 1(PARP-1)、混合系激酶域样蛋白磷酸化(pMLKL)和 gasdermin E(GSDME)。因此,EV-D68 感染会激活 caspase-8,从而触发坏死和凋亡途径。总之,我们的数据表明,caspase-8 的激活与 EV-D68 感染的 RD 细胞的炎症反应和细胞死亡有关。这一机制代表了通过抑制 caspase-8 活化来治疗 EV-D68 感染的新靶点。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Caspase-8 activation regulates enterovirus D68 infection-induced inflammatory response and cell death

Enterovirus D68 (EV-D68) infection causes severe acute respiratory infection and severe neurological complications, such as acute flaccid myelitis (AFM), in children. However, although EV-D68 has pandemic potential, no effective drugs or vaccines are currently clinically available. Furthermore, EV-D68 infection-induced inflammatory response and cell death are not fully understood. In this study, we demonstrated that several inflammatory cytokines were upregulated in a multiplicity of infection (MOI) dependent manner in EV-D68-infected human rhabdomyosarcoma (RD) cells. Quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) confirmed that tumor necrosis factor-α (TNF-α), interleukin 6 (IL-6), C-C motif chemokine ligand-5 (CCL-5), and CXC motif chemokine ligand-5 (CXCL-5) mRNA levels were highly upregulated after EV-D68 infection. IL-1β processing and maturation mediated by caspase-8 was inhibited by the caspase-8 inhibitor Z-IETD-FMK. EV-D68 infection activates caspase-8 to mediate IL-1β maturation and secretion. Additionally, EV-D68 activated cell death-related proteins such as caspase-3, poly (ADP-ribose) polymerase 1 (PARP-1), phosphorylation of Mixed Lineage Kinase domain-like protein (pMLKL), and gasdermin E (GSDME). Thus, EV-D68 infection activates caspase-8, which triggers the necroptosis and apoptosis pathways. Overall, our data suggest that caspase-8 activation is associated with the inflammatory response and cell death in EV-D68-infected RD cells. This mechanism represents a novel target for the treatment of EV-D68 infection by inhibiting caspase-8 activation.

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来源期刊
Biosafety and Health
Biosafety and Health Medicine-Infectious Diseases
CiteScore
7.60
自引率
0.00%
发文量
116
审稿时长
66 days
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