Preliminary Evidence for IL-10-Induced ACE2 mRNA Expression in Lung-Derived and Endothelial Cells: Implications for SARS-Cov-2 ARDS Pathogenesis

• DOI: 10.3389/fimmu.2021.718136
• Publication Date: 2021-09-27T18:09:00Z
• Authors: Adriana Albini; Luana Calabrone; Valentina Carlini; Nadia Benedetto; Michele Lombardo; Antonino Bruno; Douglas M. Noonan
• Keywords: Pathogenesis

Angiotensin-converting enzyme 2 (ACE2) is a receptor for the spike protein of SARS-COV-2 that allows viral binding and entry expressed on surface several pulmonary non-pulmonary cell types, with induction “cytokine storm” upon binding. Other types present can be infected, including cardiac, renal, intestinal, endothelial cells. High ACE2 levels protect from inflammation. Despite relevance in COVID-19 pathogenesis, experimental studies to comprehensively address question regulations are still limited. A relevant observation clinic that, besides pro-inflammatory cytokines, such as IL-6 IL-1β, anti-inflammatory cytokine IL-10 also elevated worse prognosis patients. This could represent somehow “danger signal”, an alarmin host organism, given immuno-regulatory properties cytokine. Here, we investigated whether increase expression lung-derived Calu-3 line. We provided preliminary evidence mRNA cells lung origin vitro , following treatment. Endothelial infection by associated vasculitis, thromboembolism, disseminated intravascular coagulation. confirmed enhancement treatment The sartans (olmesartan losartan) showed non-statistically significant modulation cells, compared untreated control observed antidiabetic biguanide metformin, putative agent, upregulates hypothesized danger signal, its elevation possibly feedback mechanism fighting Although further confirmatory required, inducing upregulation clinically COVID-19-associated acute respiratory distress syndrome (ARDS) reinforcing levels.