Effects of growth hormone/estrogen/androgen on COVID-19-type proinflammatory responses in normal human lung epithelial BEAS-2B cells

Abstract

Background COVID-19 is a disease caused by SARS-CoV-2, which can cause mild to serious infections in humans. We aimed to explore the effect of growth hormone (GH)/estrogen/androgen in normal human lung epithelial BEAS-2B cells on COVID-19-type proinflammatory responses. Methods A BEAS-2B COVID-19-like proinflammatory cell model was constructed. After that, the cells were treated with GH, 17β-estradiol (E2), and testosterone (Tes) for 24 h. CCK-8 assays were utilized to evaluate cell viability. The mRNA expression of ACE2, AGTR1, TMRRSS2, and ISG15 and the protein expression of ACE2, AGTR1, TMRRSS2, and ISG15 were measured by qRT‒PCR and Western blotting, respectively. ELISAs were performed to determine IL-6, MCP-1, MDA and SOD expression. Flow cytometry was used to measure ROS levels. Finally, MAPK/NF-κB pathway-related factor expression was evaluated. Results The COVID-19-type proinflammatory model was successfully constructed, and 1000 ng/mL RBD treatment for 24 h was selected as the condition for the model group for subsequent experiments. After RBD treatment, cell viability decreased, the mRNA expression of ACE2, AGTR1, TMRRSS2, and ISG15 and the protein expression of ACE2, AGTR1, TMRRSS2, and ISG15 increased, IL-6, MCP-1, MDA and ROS levels increased, and MDA levels decreased. The mRNA levels of MAPK14 and RELA increased, but the protein levels did not change significantly. In addition, phospho-MAPK14 and phospho-RELA protein levels were also increased. Among the tested molecules, E2 had the most pronounced effect, followed by GH, while Tes showed the opposite effect. Conclusion GH/E2 alleviated inflammation in a COVID-19-type proinflammatory model, but Tes showed the opposite effect.

Literature-Based Discovery to Elucidate the Biological Links between Resistant Hypertension and COVID-19

“…In a clinical study of 456 patients, growth hormone and IGF-1 deficiency were found in COVID-19 cases with lung involvement, regardless of age or gender; COVID-19 infection progressed worse in GH and IGF-1 deficiency [ 151 ]. Another study examining COVID-19 inflammation in cellular model found that growth hormone and estradiol improved inflammation, but testosterone had the opposite effect [ 152 ]. However, a potential complicating factor of growth hormone treatment for COVID-19 is that acromegaly, a state of endogenous GH excess, results in myocardial hypertrophy and decreased cardiac performance with increased cardiovascular mortality [ 153 ].…”