期刊
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
卷 22, 期 16, 页码 -出版社
MDPI
DOI: 10.3390/ijms22168423
关键词
COVID-19; solTNF; solTNFR1; solTNFR2; ADAM17; severity
资金
- CONACYT Mexico through the Program Estancias Posdoctorales por Mexico-COVID19.2020 [CABI1200/94/2020]
The study showed that solTNFR1 and solTNFR2 levels were elevated in COVID-19 patients without increasing transcriptional levels. SolTNFR1 was higher in severe cases and had a negative correlation with C-reactive protein, suggesting it as a potential therapeutic target. SolADAM17 levels were also higher in severe conditions, with a potential association between TNFRSF1A:rs767455 polymorphism and disease severity.
Overproduction of inflammatory cytokines is a keystone event in COVID-19 pathogenesis; TNF and its receptors (TNFR1 and TNFR2) are critical pro-inflammatory molecules. ADAM17 releases the soluble (sol) forms of TNF, TNFR1, and TNFR2. This study evaluated TNF, TNFRs, and ADAM17 at the protein, transcriptional, and gene levels in COVID-19 patients with different levels of disease severity. In total, 102 patients were divided into mild, moderate, and severe condition groups. A group of healthy donors (HD; n = 25) was included. Our data showed that solTNFR1 and solTNFR2 were elevated among the COVID-19 patients (p < 0.0001), without increasing the transcriptional level. Only solTNFR1 was higher in the severe group as compared to the mildly ill (p < 0.01), and the level was higher in COVID-19 patients who died than those that survived (p < 0.0001). The solTNFR1 level had a discrete negative correlation with C-reactive protein (p = 0.006, Rho = -0.33). The solADAM17 level was higher in severe as compared to mild disease conditions (p < 0.01), as well as in COVID-19 patients who died as compared to those that survived (p < 0.001). Additionally, a potential association between polymorphism TNFRSF1A:rs767455 and a severe degree of disease was suggested. These data suggest that solTNFR1 and solADAM17 are increased in severe conditions. solTNFR1 should be considered a potential target in the development of new therapeutic options.
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