Abstract

Background: The current Covid-19 pandemic has resulted in significant global impacts for healthcare systems and beyond. Age and or co-morbidities which are often chronic in nature are the main risk factors for severe Covid-19 infection with strong further associations with mortality. IL-6 is reported to be greatly elevated in patients with severe Covid-19 infection. As a key positive regulator for hepcidin biosynthesis this may suggest impacts for iron metabolism in these patients; elevated serum ferritin further reinforces this notion.

Aims: To investigate the effects of IL-6 and hepcidin on ACE2 gene expression in pulmonary artery endothelial cells (PAECs).

Methods: PAECs were treated with IL-6 (1-10 ng/mL) and hepcidin (0.1-1 µg/mL). Gene expression was identified by RT-PCR and Western Blot (WB).

Results: When challenged with either IL-6 or hepcidin, significant upregulation of ACE2 mRNA was observed in hPAECs (n= 3; *p<0.05). Significant elevated levels of ACE2 protein expression were also observed by western blot (n= 3; *p<0.05). In addition, knock-down of the ferroportin gene (SLC40A1) in these cells resulted in significant loss of ferroportin mRNA coupled with a strong significant up-regulation of ACE2 mRNA (n= 3; *p<0.05).

Conclusions: Whilst our results demonstrate upregulation of ACE2 gene and protein in hPAECs in response to iron regulatory elements, such as hepcidin and IL-6, further studies need to be undertaken to establish if such effects result in enhanced SARS-CoV-2 infection and whether modulation of this axis may be protective.