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. 2021 Apr;11(4):e371.
doi: 10.1002/ctm2.371.

Interactions between ibuprofen, ACE2, renin-angiotensin system, and spike protein in the lung. Implications for COVID-19

Rita Valenzuela  1   2 , Maria A Pedrosa  1   2 , Pablo Garrido-Gil  1   2 , Carmen M Labandeira  1   3 , Gemma Navarro  2   4 , Rafael Franco  2   5 , Ana I Rodriguez-Perez  1   2 , Jose L Labandeira-Garcia  1   2
Affiliations

Interactions between ibuprofen, ACE2, renin-angiotensin system, and spike protein in the lung. Implications for COVID-19

Rita Valenzuela et al. Clin Transl Med. 2021 Apr.
No abstract available

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Conflict of interest statement

The authors declare that there is no conflict of interest.

Figures

FIGURE 1
FIGURE 1
Effects of ibuprofen on mRNA (A,D) and protein (B,E) expression of ACE2 and AT1, AT2 and Mas receptors, ACE2 enzymatic activity (C), and levels of AngII (F) and Ang1–7 (G) in the lung of healthy adult rats (A–C) and rat models of metabolic syndrome (MetS; D–G). Data are mean ± SEMs. *p < .05 Relative to control adult rats; #p < .05 relative to untreated rat models of metabolic syndrome. For two groups comparisons Student's test or Mann–Whitney rank sum test were used. One‐way analysis of variance (ANOVA) with Student–Newman–Keuls method post hoc test or Kruskal–Wallis one‐way ANOVA on ranks with Student–Newman–Keuls method post hoc test were used for multiple comparisons
FIGURE 2
FIGURE 2
Cultures of human alveolar type‐II A549 pneumocytes. Effects of 24 or 48 h treatment with ibuprofen on cellular ACE2 mRNA expression (A). Levels of ACE2 protein (B,D,E) and enzymatic activity (C) in cells (B–D) and culture medium (E) of cultures treated with spike protein alone or spike protein and ibuprofen. Laser confocal microphotographs that show fluorescent labeling for ACE2 (green, F), spike protein (red, G), and colocalization of ACE2 and spike (H, yellow) in pneumocytes treated with spike protein. *p < .05 Relative to untreated controls; #p < .05 relative to cells treated with spike alone (one‐way analysis of variance [ANOVA] with Student–Newman–Keuls method post hoc test or Kruskal–Wallis one‐way ANOVA on ranks with Student–Newman–Keuls method post hoc test). Scale bar (for F–H): 25 μm
FIGURE 3
FIGURE 3
Cultures of human alveolar type‐II A549 pneumocytes. Effects of ibuprofen on the level of SARS‐CoV‐2 spike RBD‐Fc internalization quantified as cell fluorescence intensity using a laser confocal microscope (A–J). Fluorescent labeling for ACE2 (green), spike protein (red), and colocalization of ACE2 and spike (yellow) in cells not treated with spike (A–C), cells treated with spike protein only (D–F), and cells treated with spike protein and ibuprofen (G–I). Levels of TNF‐α (K), IL‐6 (L), CCL‐2 (M) in human alveolar type‐II A549 pneumocytes treated with spike protein only or spike protein and ibuprofen. ADAM17 (N) and TMPRSS2 (O) enzymatic activities in human alveolar type‐II A549 pneumocytes treated with spike protein alone or spike protein together with ibuprofen.*p < .05 Relative to untreated controls; #p < .05 relative to cells treated with spike alone (one‐way analysis of variance [ANOVA] with Student–Newman–Keuls method post hoc test or Kruskal–Wallis one‐way ANOVA on ranks with Student–Newman–Keuls method post hoc test). Scale bar (for all photographs): 25 μm
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