SARS-CoV-2 spike protein S1 subunit induces pro-inflammatory responses via toll-like receptor 4 signaling in murine and human macrophages.
SARS-CoV-2 spike protein S1 subunit induces pro-inflammatory responses via toll-like receptor 4 signaling in murine and human macrophages.
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SARS-CoV-2刺突蛋白S1亚基通过Toll样受体4信号转导诱导小鼠和人巨噬细胞的促炎反应
DOI：
10.1016/j.heliyon.2021.e06187
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发表时间：
2021-03
期刊：
影响因子：
4
通讯作者：
Kizaki T
中科院分区：
文献类型：
--
作者：
Shirato K;Kizaki T
2019冠状病毒病（COVID-19）是由严重急性呼吸系统综合征冠状病毒2 （SARS-CoV-2）引起的传染病，目前已在全球蔓延。一些患者会出现严重的并发症，包括多器官衰竭。有研究表明，与疾病相关的过度炎症在COVID-19的严重程度和死亡率中起着重要作用。为了阐明COVID-19涉及的炎症机制，我们研究了SARS-CoV-2刺突蛋白S1亚基（以下简称S1）对小鼠和人巨噬细胞的促炎反应的影响。小鼠腹腔渗出巨噬细胞对S1暴露产生促炎介质。暴露于S1也激活了核因子-κB （NF-κB）和c-Jun n -末端激酶（JNK）信号通路。NF-κB和JNK通路的选择性抑制剂抑制了S1对促炎细胞因子的诱导。toll样受体4 （TLR4）拮抗剂治疗小鼠腹腔渗出巨噬细胞和人THP-1细胞源性巨噬细胞可减弱促炎细胞因子的诱导和S1和脂多糖对细胞内信号的激活。TLR4 sirna转染小鼠RAW264.7巨噬细胞的实验也得到了类似的结果。相比之下，TLR2中和抗体不能消除s1诱导的RAW264.7或THP-1细胞源性巨噬细胞的促炎细胞因子诱导。这些结果表明，SARS-CoV-2刺突蛋白S1亚基激活TLR4信号，诱导小鼠和人巨噬细胞的促炎反应。因此，巨噬细胞中的TLR4信号可能是调节COVID-19患者过度炎症的潜在靶点。SARS-CoV-2，刺突蛋白，S1亚基，toll样受体4，炎症，巨噬细胞
Coronavirus disease 2019 (COVID-19), an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has now spread globally. Some patients develop severe complications including multiple organ failure. It has been suggested that excessive inflammation associated with the disease plays major role in the severity and mortality of COVID-19. To elucidate the inflammatory mechanisms involved in COVID-19, we examined the effects of SARS-CoV-2 spike protein S1 subunit (hereafter S1) on the pro-inflammatory responses in murine and human macrophages. Murine peritoneal exudate macrophages produced pro-inflammatory mediators in response to S1 exposure. Exposure to S1 also activated nuclear factor-κB (NF-κB) and c-Jun N-terminal kinase (JNK) signaling pathways. Pro-inflammatory cytokine induction by S1 was suppressed by selective inhibitors of NF-κB and JNK pathways. Treatment of murine peritoneal exudate macrophages and human THP-1 cell-derived macrophages with a toll-like receptor 4 (TLR4) antagonist attenuated pro-inflammatory cytokine induction and the activation of intracellular signaling by S1 and lipopolysaccharide. Similar results were obtained in experiments using TLR4 siRNA-transfected murine RAW264.7 macrophages. In contrast, TLR2 neutralizing antibodies could not abrogate the S1-induced pro-inflammatory cytokine induction in either RAW264.7 or THP-1 cell-derived macrophages. These results suggest that SARS-CoV-2 spike protein S1 subunit activates TLR4 signaling to induce pro-inflammatory responses in murine and human macrophages. Therefore, TLR4 signaling in macrophages may be a potential target for regulating excessive inflammation in COVID-19 patients. SARS-CoV-2, Spike protein, S1 subunit, Toll-like receptor 4, Inflammation, Macrophage
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影响因子：
64.8
作者：
Li W;Moore MJ;Vasilieva N;Sui J;Wong SK;Berne MA;Somasundaran M;Sullivan JL;Luzuriaga K;Greenough TC;Choe H;Farzan M
通讯作者：
Farzan M
DOI：
10.1155/2018/5072986
发表时间：
2018
期刊：
Evidence-based complementary and alternative medicine : eCAM
影响因子：
--
作者：
Shirato K;Koda T;Takanari J;Sakurai T;Ogasawara J;Imaizumi K;Ohno H;Kizaki T
通讯作者：
Kizaki T
影响因子：
4.4
作者：
Roelofs, MF;Boelens, WC;Radstake, TRDJ
通讯作者：
Radstake, TRDJ
影响因子：
4.4
作者：
Ohashi, K;Burkart, V;Kolb, H
通讯作者：
Kolb, H
影响因子：
4.8
作者：
Okamura, Y;Watari, M;Strauss, JF
通讯作者：
Strauss, JF