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基于转录组学特征的方法研究催产素在 COVID-19 中的抗炎和免疫促进作用。

Oxytocin's anti-inflammatory and proimmune functions in COVID-19: a transcriptomic signature-based approach.

机构信息

University of Toledo, Department of Neurosciences, College of Medicine and Life Sciences, Toledo, Ohio.

University of Toledo, Department of Psychiatry, College of Medicine and Life Sciences, Toledo, Ohio.

出版信息

Physiol Genomics. 2020 Sep 1;52(9):401-407. doi: 10.1152/physiolgenomics.00095.2020. Epub 2020 Aug 18.

Abstract

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a worldwide pandemic, infecting over 16 million people worldwide with a significant mortality rate. However, there is no current Food and Drug Administration-approved drug that treats coronavirus disease 2019 (COVID-19). Damage to T lymphocytes along with the cytokine storm are important factors that lead to exacerbation of clinical cases. Here, we are proposing intravenous oxytocin (OXT) as a candidate for adjunctive therapy for COVID-19. OXT has anti-inflammatory and proimmune adaptive functions. Using the Library of Integrated Network-Based Cellular Signatures (LINCS), we used the transcriptomic signature for carbetocin, an OXT agonist, and compared it to gene knockdown signatures of inflammatory (such as interleukin IL-1β and IL-6) and proimmune markers (including T cell and macrophage cell markers like CD40 and ARG1). We found that carbetocin's transcriptomic signature has a pattern of concordance with inflammation and immune marker knockdown signatures that are consistent with reduction of inflammation and promotion and sustaining of immune response. This suggests that carbetocin may have potent effects in modulating inflammation, attenuating T cell inhibition, and enhancing T cell activation. Our results also suggest that carbetocin is more effective at inducing immune cell responses than either lopinavir or hydroxychloroquine, both of which have been explored for the treatment of COVID-19.

摘要

严重急性呼吸综合征冠状病毒 2(SARS-CoV-2)已在全球范围内引发大流行,感染了全球超过 1600 万人,死亡率较高。然而,目前还没有获得美国食品和药物管理局批准的药物可以治疗 2019 年冠状病毒病(COVID-19)。T 淋巴细胞的损伤以及细胞因子风暴是导致临床病例恶化的重要因素。在这里,我们建议将静脉内催产素(OXT)作为 COVID-19 辅助治疗的候选药物。OXT 具有抗炎和免疫适应性功能。使用基于整合网络的细胞信号文库(LINCS),我们使用了卡贝缩宫素(一种 OXT 激动剂)的转录组特征,并将其与炎症(如白细胞介素 IL-1β 和 IL-6)和免疫标志物(包括 T 细胞和巨噬细胞标志物,如 CD40 和 ARG1)的基因敲低特征进行了比较。我们发现卡贝缩宫素的转录组特征与炎症和免疫标志物敲低特征具有一致性,这表明卡贝缩宫素可能具有调节炎症、减弱 T 细胞抑制和增强 T 细胞激活的强大作用。我们的研究结果还表明,卡贝缩宫素在诱导免疫细胞反应方面比洛匹那韦或羟氯喹更有效,这两种药物都已被探索用于治疗 COVID-19。

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