The Expression Levels of SARS-CoV-2 Infection-Mediating Molecules Promoted by Interferon-γ and Tumor Necrosis Factor-α Are Downregulated by Hydrogen Sulfide

Abstract

Autoimmune thyroid diseases (AITDs), which include Hashimoto’s thyroiditis (HT) and Graves’ disease (GD), have a higher prevalence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in the literature. The effects of AITD-associated cytokines on SARS-CoV-2 infection-mediating molecule levels might be involved in the pathogenesis of susceptibility. We speculated that hydrogen sulfide (H2S) might attenuate this process since H2S has antiviral effects. Using immunohistochemistry, we found that angiotensin-converting enzyme-II (ACE2) expression was higher in the HT group and neuropilin 1 (NRP1) expression was higher in HT and GD groups than in the normal group, while transmembrane protease serine type 2 (TMPRSS2) expression was lower in HT and GD groups. When culturing primary thyrocytes with cytokines or sodium hydrosulfide (NaHS) plus cytokines, we found that ACE2 and NRP1 mRNA levels were upregulated while TMPRSS2 levels were downregulated by interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α). After pretreatment with NaHS in thyrocytes, ACE2 and NRP1 expression were downregulated compared to IFN-γ or TNF-α treatment, and NaHS had no effect on TMPRSS2 expression. Our findings suggested that IFN-γ and TNF-α, which are elevated in AITDs, promoted ACE2 and NRP1 expression and inhibited TMPRSS2 expression. H2S might protect against SARS-CoV-2 infection by downregulating ACE2 and NRP1 levels.