坏死性下垂
呼吸上皮
上睑下垂
程序性细胞死亡
生物
免疫学
细胞因子
上皮
细胞凋亡
冠状病毒
病毒学
细胞生物学
医学
疾病
病理
2019年冠状病毒病(COVID-19)
传染病(医学专业)
生物化学
遗传学
作者
Siyuan Hao,Kang Ning,Çağla Aksu Küz,Min Xiong,Wei Zou,Soo Y. Park,Shane McFarlin,Ziying Yan,Jianming Qiu
摘要
Abstract Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) is the cause the ongoing pandemic of coronavirus disease 2019 (COVID19). One key feature associated with COVID‐19 is excessive pro‐inflammatory cytokine production that leads to severe acute respiratory distress syndrome. Although the cytokine storm induces inflammatory cell death in the host, which type of programmed cell death mechanism that occurs in various organs and cells remains elusive. Using an in vitro culture model of polarized human airway epithelium (HAE), we observed that necroptosis, but not apoptosis or pyroptosis, plays an essential role in the damage of the epithelial barrier of polarized HAE infected with SARS‐CoV‐2. Pharmacological inhibitors of necroptosis, necrostatin‐2 and necrosulfonamide, efficiently prevented cell death and epithelial barrier dysfunction caused by SARS‐CoV‐2 infection. Moreover, the silencing of genes that are involved in necroptosis, RIPK1 , RIPK3 , and MLKL , ameliorated airway epithelial damage of the polarized HAE infected with SARS‐CoV‐2. This study, for the first time, confirms that SARS‐CoV‐2 infection triggers necroptosis that disrupts the barrier function of human airway epithelia in vitro.
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