Vitamin D and interferon-γ co-operate to increase the ACE-2 receptor expression in primary cultures of human thyroid cells

• Published in: Journal of endocrinological investigation 2022-11, Vol.45 (11), p.2157-2163
• Main Authors: Coperchini, F., Greco, A., Denegri, M., Ripepi, F. A., Grillini, B., Bertini, J., Calì, B., Villani, L., Magri, F., Croce, L., Gaetano, C., Cappelli, C., Trimboli, P., Chiovato, L., Rotondi, M.
• Format: Article
• Language: English
• Subjects: ACE2; Angiotensin; Angiotensin-converting enzyme 2; Cell membranes; Coronaviruses; COVID-19; Endocrinology; Immune system; Immunocytochemistry; Internal Medicine; Medicine; Medicine & Public Health; Membrane proteins; Metabolic Diseases; mRNA; Original; Original Article; Peptidyl-dipeptidase A; Polymerase chain reaction; Severe acute respiratory syndrome coronavirus 2; Supplements; Thyrocytes; Thyroid; Thyroid gland; Vitamin D; γ-Interferon
• ISSN: 1720-8386; 0391-4097; 1720-8386
• DOI: 10.1007/s40618-022-01857-9

Background A more severe course of COVID-19 was associated with low levels of Vitamin D (VitD). Moreover in vitro data showed that VitD up-regulates the mRNA of the Angiotensin Converting Enzyme 2 (ACE-2), the SARS-COV-2 receptor in different type of cells. ACE-2 is expressed in several type of tissues including thyroid cells, on which its mRNA was shown to be up-regulated by interferon-gamma (IFN-γ). The aim of the present study was to investigate if treatment with VitD alone or in combination with IFN-γ would increase ACE-2 both at mRNA and protein levels in primary cultures of human thyrocytes. Materials and methods Primary thyroid cell cultures were treated with VitD and IFN-γ alone or in combination for 24 h. ACE-2 mRNA levels were measured by Real-time Polymerase Chain Reaction (RT-PCR). The presence of ACE-2 on thyroid cell membrane was assessed by immunocytochemistry basally and after the previous mentioned treatments. Results ACE-2 mRNA levels increased after treatment with VitD and IFN-γ alone. The combination treatment (VitD + IFN-γ) showed an additive increase of ACE-2-mRNA. Immunocytochemistry experiments showed ACE-2 protein on thyroid cells membrane. ACE-2 expression increased after treatment with VitD and IFN-γ alone and further increased by the combination treatment with VitD + IFN-γ. Conclusions VitD would defend the body by SARS-COV2 both by regulating the host immune defense and by up-regulating of the expression of the ACE-2 receptor. The existence of a co-operation between VitD and IFN-γ demonstrated in other systems is supported also for ACE-2 up-regulation. These observations lead to an increased interest for the potential therapeutic benefits of VitD supplementation in COVID-19.