Effect of Therapeutics on the Modulation of ACE2 Expression in Airway Epithelium: Implications for COVID-19
| Autor: | Don D. Sin, G. K. Singhera, T. Guo, Janice M. Leung, Delbert R. Dorscheid |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
business.industry
Captopril Hydroxychloroquine Ciclesonide Pharmacology chemistry.chemical_compound medicine.anatomical_structure Losartan chemistry medicine Respiratory epithelium Telmisartan business hormones hormone substitutes and hormone antagonists Dexamethasone medicine.drug Respiratory tract |
| Zdroj: | TP3. TP003 COVID-19 INFECTIONS, MECHANISMS, AND CLINICAL IMPLICATIONS. |
| DOI: | 10.1164/ajrccm-conference.2021.203.1_meetingabstracts.a1283 |
| Popis: | RATIONALE: Coronavirus disease 2019 (COVID-19) is a global pandemic caused by severe acute respiratory syndrome coronavirus (SARS-CoV2). SARS-CoV-2 uses the receptor angiotensin-converting enzyme 2 (ACE2) to gain entry to host cells in the respiratory tract epithelium. Clinical features post viral infection include symptoms of viral pneumonia, fever, cough, chest discomfort, and in severe cases dyspnea and bilateral lung infiltration. Adults with any age are at risk of getting COVID-19, however co-morbidities like hypertension, COPD, smoking, type 2 diabetes, asthma, obesity etc. increase infection susceptibility. Modern day therapeutics to control aforementioned health conditions include angiotensin II receptor blockers (ARBs), ACE inhibitors (ACEi), and anti-inflammatory drugs such as dexamethasone and hydroxychloroquine. Since binding of viral spike protein with receptor ACE2 initiates viral entry in the host, hence ACE2 has been one of the main candidates to understand the mechanism of viral infection. In this study our aim was to investigate if ACE2 expression levels can be modulated with therapeutic interventions. Methods: In an in vitro model of monolayer cultures, human airway epithelial (1HAEo-) cell lines were treated with losartan and telmisartan (ARB), captopril (ACEi), and hydroxychloroquine at half-log concentrations from 1 to 100 μM, and fluticasone, ciclesonide, and dexamethasone (steroids) at half-log concentrations from 0.3 to 10 μM. Whole cell lysates were obtained at 24hr post-treatment to quantify ACE2 expression via western blotting. Statistical analysis was performed using one-way ANOVA and Dunnett's multiple comparison test. Results: The in vitro experiments have shown that total ACE2 protein expression in 1HAEo-cells is modulated in response to certain drugs. Compared to untreated control cells, losartan treatment showed ∼45 % significant increase in ACE2 expression at both 3 μM and 10 μM concentrations (p< 0.01), whereas dexamethasone showed ∼ 40% significant increase at 10 μM dose (p< 0.001). Captopril treatment showed ∼35% decrease at 30 and 100 μM (p |
| Databáze: | OpenAIRE |
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