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. 2022 Mar 5;100(4):613–627. doi: 10.1007/s00109-022-02182-7

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© The Author(s) 2022

Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

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Fig. 3 — B₂R-antagonism exhibits a protective and suppressive effect on gene expression profile of airway epithelial cells. A Volcano plots showing global gene expression changes induced by either treatment with B₂R-antagonist or hydrocortisone (HC). Red indicates significantly upregulated entities; blue indicates significantly downregulated entities. Gene expression analysis of pre-treated NHBEs after 24 h of SARS-CoV-2-infection. B Heat map of gene expression analysis of genes involved in the epithelial antiviral response, analysis of the effects of SARS-CoV-2-infection. Only entities with significant changes between SARS-CoV-2-infection and medium are shown (gene expression fold change FC ≥ 1.5 with P < 0.05). C Heat map of gene expression analysis of genes involved in the acute-phase response is depicted. All entities are shown. Asterisks indicate significantly regulated genes (P < 0.05) in SARS-CoV-2 compared to medium. D Heat map of gene expression analysis of known and potential virus entry receptors is depicted. All entities are shown. Color code indicates Log2-fold change from low (blue) through 0 (white) to high (red). Asterisks indicate significantly regulated genes (P < 0.05) in SARS-CoV-2-infected NHBEs compared to medium. Duplicate gene names indicate the presence of two or more isoforms of the same gene in the analysis. E Analysis of TMPRSS2 gene expression by qPCR after 24 h of pre-treatment with/without 10 μM hydrocortisone (HC) followed by 24 h of SARS-CoV-2 inoculation. Red indicates SARS-CoV-2-infection; yellow indicates pre-treatment with hydrocortisone (HC). Statistical tests compared SARS-CoV-2-infected versus uninfected samples or B₂R-antagonist-treated versus untreated samples. F Quantification of infectious particles in the supernatants of SARS-CoV-2-infected NHBEs from 10 donors that were pre-treated with/without 10 μM hydrocortisone (HC) for 24 h. Supernatants were titrated on Vero-E6 cells. The plaque assay was quantified 24 h later. Results are depicted as plaque-forming units (PFU) per milliliter