Effect of SARS-CoV-2 spike protein exposure on ACE2 and interleukin 6 productions in human adipocytes: An in-vitro study

Narra J Pub Date : 2023-10-29 DOI:10.52225/narra.v3i3.284
Meity Ardiana, I GR. Suryawan, Hanestya O. Hermawan, Primasitha M. Harsono, Aisya A. Shafira, Faizal A. Anandita
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Abstract

Since adipocytes play a crucial role in pathogenesis of severe acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2) infection due to their interaction with angiotensin-converting enzyme 2 (ACE2) and interleukin 6 (IL-6), obesity is associated with an increased risk of coronavirus disease 2019 (COVID-19) mortality. Discovery of ACE2 as a SARS-CoV-2 receptor raises a controversy about whether to use ACE inhibitors (ACEIs) could be an optional therapy to prevent cytokine storms. Studies assessing the expressions of ACE2 and IL-6 upon exposure to SARS‑CoV‑2 is therefore important as a basis for therapeutical trials in the future. The aim of this study was to determine the effect of SARS-CoV-2 spike protein exposure on the production of ACE2 and IL-6 in adipocyte cells. Adipocytes were collected from abdominal adipose tissues of healthy and obese 45-year-old male donor having neither a history of SARS‑CoV‑2 infection nor COVID-19 vaccination. After being stained using the oil red O protocol, the viable adipocytes were then exposed to S1 subunit of SARS-CoV-2 spike protein. The levels of ACE2 and IL-6 were then examined using the enzyme-linked immunosorbent assay (ELISA). The results showed significant increase of ACE2 (90.22 µg/mL) and IL-6 level (60.01 µg/mL) in human adipocytes upon exposure compared to unexposed control cells (ACE2 13.33 µg/mL; IL-6 21.33 µg/mL), both comparisons had p<0.001). This study provides insight into the basic mechanism of severe COVID-19 symptoms in obese patients and provides a basic information of the potential of ACE inhibitors as an optional therapy for COVID-19 patients with obesity.
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SARS-CoV-2刺突蛋白暴露对人脂肪细胞中ACE2和白细胞介素6产生的影响:一项体外研究
由于脂肪细胞与血管紧张素转换酶2 (ACE2)和白细胞介素6 (IL-6)相互作用,在严重急性呼吸综合征冠状病毒2 (SARS - CoV - 2)感染的发病机制中起着至关重要的作用,因此肥胖与2019年冠状病毒病(COVID-19)死亡风险增加有关。ACE2作为SARS-CoV-2受体的发现引发了关于使用ACE抑制剂(ACEIs)是否可以作为预防细胞因子风暴的可选治疗的争议。因此,评估暴露于SARS - CoV - 2后ACE2和IL-6表达的研究作为未来治疗试验的基础是重要的。本研究的目的是确定暴露于SARS-CoV-2刺突蛋白对脂肪细胞中ACE2和IL-6产生的影响。脂肪细胞采集自既无SARS - CoV - 2感染史也无COVID-19疫苗接种史的45岁健康和肥胖男性供体的腹部脂肪组织。用油红O染色后,将活的脂肪细胞暴露于SARS-CoV-2刺突蛋白S1亚基。然后用酶联免疫吸附试验(ELISA)检测ACE2和IL-6的水平。结果显示,与未暴露的对照细胞(ACE2 13.33µg/mL; ACE2 13.33µg/mL;IL-6 21.33µg/mL),两组比较均为p<0.001)。本研究揭示了肥胖患者COVID-19严重症状的基本机制,并为ACE抑制剂作为COVID-19肥胖患者可选治疗的潜力提供了基本信息。
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