Cannabidiol inhibits SARS-Cov-2 spike (S) protein-induced cytotoxicity and inflammation through a PPARγ-dependent TLR4/NLRP3/Caspase-1 signaling suppression in Caco-2 cell line.
Cannabidiol inhibits SARS-Cov-2 spike (S) protein-induced cytotoxicity and inflammation through a PPARγ-dependent TLR4/NLRP3/Caspase-1 signaling suppression in Caco-2 cell line.
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DOI：
10.1002/ptr.7302
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发表时间：
2021-12
期刊：
影响因子：
--
通讯作者：
Esposito G
中科院分区：
文献类型：
--
作者：
Corpetti C;Del Re A;Seguella L;Palenca I;Rurgo S;De Conno B;Pesce M;Sarnelli G;Esposito G
鉴于血管紧张素转换酶2（ACE-2）受体密度的降低，除了肺，肠道被认为是冠状病毒2型严重急性呼吸综合征（SARS-CoV-2）感染和复制的替代部位。大麻二酚（CBD）最近被提议用于管理2019冠状病毒病（COVID-19）呼吸道症状，因为它在肺部具有抗炎和免疫调节活性。在这项研究中，我们证明了CBD（10 - 9 - 10 - 7 M）在Caco-2细胞中预防SARS-CoV-2刺突蛋白（SP）引发的上皮损伤和炎症反应的体外PPAR-γ依赖性功效。免疫印迹分析显示，CBD能够减少由SP孵育触发的所有分析的促炎标志物，例如工具样受体4（TLR-4）、ACE-2、Ras同源物A-GT β（RhoA-GT β）的家族成员、炎性小体复合物（NLRP 3）和Caspase-1。通过酶联免疫吸附测定（ELISA）测定，CBD引起白细胞介素1 β（IL-1β）、IL-6、肿瘤坏死因子α（TNF-α）和IL-18的平行抑制。通过免疫荧光分析，我们观察到CBD治疗后紧密连接蛋白的表达增加和跨上皮电阻（TEER）的恢复，以及由SP诱导的异硫氰酸荧光素（FITC）-葡聚糖渗透性的拯救。总之，我们的数据表明，CBD是体外SP蛋白肠毒性的强大抑制剂。
Given the abundancy of angiotensin converting enzyme 2 (ACE‐2) receptors density, beyond the lung, the intestine is considered as an alternative site of infection and replication for severe acute respiratory syndrome by coronavirus type 2 (SARS‐CoV‐2). Cannabidiol (CBD) has recently been proposed in the management of coronavirus disease 2019 (COVID‐19) respiratory symptoms because of its anti‐inflammatory and immunomodulatory activity exerted in the lung. In this study, we demonstrated the in vitro PPAR‐γ‐dependent efficacy of CBD (10−9‐10−7 M) in preventing epithelial damage and hyperinflammatory response triggered by SARS‐CoV‐2 spike protein (SP) in a Caco‐2 cells. Immunoblot analysis revealed that CBD was able to reduce all the analyzed proinflammatory markers triggered by SP incubation, such as tool‐like receptor 4 (TLR‐4), ACE‐2, family members of Ras homologues A‐GTPase (RhoA‐GTPase), inflammasome complex (NLRP3), and Caspase‐1. CBD caused a parallel inhibition of interleukin 1 beta (IL‐1β), IL‐6, tumor necrosis factor alpha (TNF‐α), and IL‐18 by enzyme‐linked immunosorbent assay (ELISA) assay. By immunofluorescence analysis, we observed increased expression of tight‐junction proteins and restoration of transepithelial electrical resistance (TEER) following CBD treatment, as well as the rescue of fluorescein isothiocyanate (FITC)–dextran permeability induced by SP. Our data indicate, in conclusion, that CBD is a powerful inhibitor of SP protein enterotoxicity in vitro.
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超微粉化棕榈酰乙醇酰胺可抑制培养的小鼠肺泡巨噬细胞中 NLRP3 炎症小体的表达和由 SARS-CoV-2 刺突蛋白激活的促炎症反应。
影响因子：
4.1
作者：
Del Re A;Corpetti C;Pesce M;Seguella L;Steardo L;Palenca I;Rurgo S;De Conno B;Sarnelli G;Esposito G
通讯作者：
Esposito G
影响因子：
11.8
作者：
Du, Pengcheng;Song, Chuan;Zeng, Hui
通讯作者：
Zeng, Hui
影响因子：
15.3
作者：
Ding, Xiaomeng;Hu, Xiaoyi;Yu, Qiang
通讯作者：
Yu, Qiang
影响因子：
5.6
作者：
Cocetta V;Governa P;Borgonetti V;Tinazzi M;Peron G;Catanzaro D;Berretta M;Biagi M;Manetti F;Dall'Acqua S;Montopoli M
通讯作者：
Montopoli M
DOI：
10.1124/jpet.120.000479
发表时间：
2021-05-01
影响因子：
3.5
作者：
Berg, Barbara Betonico;Soares, Jaqueline Silva;Miranda e Castor, Marina Gomes
通讯作者：
Miranda e Castor, Marina Gomes