15-lipoxygenase and cyclooxygenase expression profile and their related modulators in COVID-19 infection

Sara Kianfar , Vahid Salimi , Alireza Jahangirifard , Seyed Bashir Mirtajani , Mohammad Amin Vaezi , Jila Yavarian , Talat Mokhtari-Azad , Masoumeh Tavakoli-Yaraki
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Abstract

Background

The role of the lipoxygenase (LOX) and cyclooxygenase (COX) enzymes in maintaining cellular homeostasis and regulating immune responses promoted us in this study to analyze the pattern of changes in 15-lipoxygenase and cyclooxygenase isoforms and their related cytokines in SARS-CoV-2 infection.

Methods

15-LOX-1, 15-LOX-2, COX-1 and COX-2 gene expression levels were determined using qRT-PCR in nasopharynx specimens from patients with severe [N = 40] and non-severe [N = 40] confirmed SARS-CoV-2 infections and healthy controls. Circulating levels of lL-6, lL-10, PGE2, and IFN-γ were measured in patients and healthy controls using ELISA assay. The associations between the measured variables and the patient's clinic-pathological characteristics were assessed for all groups.

Results

The expression level of 15-LOX-1 was elevated significantly in male patients with severe infection; although female patients showed a different expression profile. 15-LOX-2 expression level was considerably increased in male patients with severe infection; while changes in its expression remained inconclusive in female patients. The relationship between 15-LOX expression and the male gender was prominent. Both COX isoforms expression showed elevation in male and female patients that were correlated with disease severity. The simultaneous increase in lL-6, PGE2 and IFN-γ levels also decrease in lL-10 in patients with severe infection indicating the possible regulatory network related to the COX and 15-LOX enzymes in the output of the SARS-CoV-2 infection.

Conclusion

The results of this study determined the pattern of possible changes in key enzymes of prostaglandin and eicosanoids synthesis pathway and their mediators, which can be helpful in mapping the SARS-CoV-2 pathogenicity and pharmaceutical approaches.

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15-脂氧合酶和环氧合酶在新冠肺炎感染中的表达谱及其相关调节剂。
背景:脂氧合酶(LOX)和环氧合酶(COX)在维持细胞稳态和调节免疫反应中的作用促使我们在本研究中分析了严重急性呼吸系统综合征冠状病毒2型感染中15种脂氧合蛋白和环氧合蛋白亚型及其相关细胞因子的变化模式。方法:采用qRT-PCR方法测定严重和非严重确诊的严重急性呼吸系统综合征冠状病毒2型感染者和健康对照者鼻咽标本中15-LOX-1、15-LOX-2、COX-1和COX-2基因的表达水平。用ELISA法测定患者和健康对照组的循环中lL-6、lL-10、PGE2和IFN-γ的水平。对所有组的测量变量与患者临床病理特征之间的相关性进行了评估。结果:15-LOX-1在男性重症感染患者中的表达水平显著升高;尽管女性患者表现出不同的表达谱。15-LOX-2的表达水平在患有严重感染的男性患者中显著增加;而在女性患者中其表达的变化仍不确定。15-LOX的表达与男性的关系显著。两种COX亚型在男性和女性患者中的表达均升高,这与疾病的严重程度相关。严重感染患者的lL-6、PGE2和IFN-γ水平同时升高,lL-10水平也降低,这表明可能与严重急性呼吸系统综合征冠状病毒2型感染输出中的COX和15-LOX酶有关的调节网络。结论:本研究结果确定了前列腺素和类二十烷合成途径关键酶及其介质的可能变化模式,有助于绘制严重急性呼吸系统综合征冠状病毒2型的致病性和药物途径。
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来源期刊
Prostaglandins, leukotrienes, and essential fatty acids
Prostaglandins, leukotrienes, and essential fatty acids Clinical Biochemistry, Endocrinology, Diabetes and Metabolism
CiteScore
5.30
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0.00%
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0
审稿时长
64 days
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