Human Bronchial Epithelial Cell Transcriptome Changes in Response to Serum from Patients with Different Status of Inflammation

• Published in: Lung Vol. 202; no. 2; pp. 157 - 170
• Main Authors: Sivaraman, Kokilavani, Liu, Bin, Martinez-Delgado, Beatriz, Held, Julia, Büttner, Manuela, Illig, Thomas, Volland, Sonja, Gomez-Mariano, Gema, Jedicke, Nils, Yevsa, Tetyana, Welte, Tobias, DeLuca, David S., Wrenger, Sabine, Olejnicka, Beata, Janciauskiene, Sabina
• Format: Journal Article
• Language: English
• Published: New York Springer US 01-04-2024; Springer Nature B.V
• Subjects: ACE2; Angiotensin-converting enzyme 2; Biomarkers - metabolism; Carbon dioxide; Cell culture; COVID-19; Cytoskeleton; E-cadherin; E-selectin; Epithelial cells; Epithelial Cells - metabolism; Epithelium; Gene regulation; Genes; Humans; Illnesses; Immunoassay; Inflammation; Inflammation - genetics; Inflammation - metabolism; Kinases; Lung Inflammation; Medicine; Medicine & Public Health; Monocyte chemoattractant protein 1; Patients; Pneumology/Respiratory System; Principal components analysis; Ribonucleic acid; RNA; Serum levels; TLR4 protein; Toll-like receptors; Transcriptome; Transcriptomes; Immune hyper-activation; RNA-seq; Gene expression; Acute lung inflammation; Chemokine/cytokine profile
• ISSN: 0341-2040; 1432-1750
• DOI: 10.1007/s00408-024-00679-1

Purpose
To investigate the transcriptome of human bronchial epithelial cells (HBEC) in response to serum from patients with different degrees of inflammation.
Methods
Serum from 19 COVID-19 patients obtained from the Hannover Unified Biobank was used. At the time of sampling, 5 patients had a WHO Clinical Progression Scale (WHO-CPS) score of 9 (severe illness). The remaining 14 patients had a WHO-CPS of below 9 (range 1–7), and lower illness. Multiplex immunoassay was used to assess serum inflammatory markers. The culture medium of HBEC was supplemented with 2% of the patient’s serum, and the cells were cultured at 37 °C, 5% CO
2
for 18 h. Subsequently, cellular RNA was used for RNA-Seq.
Results
Patients with scores below 9 had significantly lower albumin and serum levels of E-selectin, IL-8, and MCP-1 than patients with scores of 9. Principal component analysis based on 500 “core genes” of RNA-seq segregated cells into two subsets: exposed to serum from 4 (I) and 15 (II) patients. Cells from a subset (I) treated with serum from 4 patients with a score of 9 showed 5566 differentially expressed genes of which 2793 were up- and 2773 downregulated in comparison with cells of subset II treated with serum from 14 patients with scores between 1 and 7 and one with score = 9. In subset I cells, a higher expression of
TLR4
and
CXCL8
but a lower
CDH1
,
ACE2
, and
HMOX1
, and greater effects on genes involved in metabolic regulation, cytoskeletal organization, and kinase activity pathways were observed.
Conclusion
This simple model could be useful to characterize patient serum and epithelial cell properties.