Global Transcriptome Analysis Reveals Distinct Phases of the Endothelial Response to TNF.
J Immunol
; 212(1): 117-129, 2024 01 01.
Article
en En
| MEDLINE
| ID: mdl-38019121
ABSTRACT
The vascular endothelium acts as a dynamic interface between blood and tissue. TNF-α, a major regulator of inflammation, induces endothelial cell (EC) transcriptional changes, the overall response dynamics of which have not been fully elucidated. In the present study, we conducted an extended time-course analysis of the human EC response to TNF, from 30 min to 72 h. We identified regulated genes and used weighted gene network correlation analysis to decipher coexpression profiles, uncovering two distinct temporal phases an acute response (between 1 and 4 h) and a later phase (between 12 and 24 h). Sex-based subset analysis revealed that the response was comparable between female and male cells. Several previously uncharacterized genes were strongly regulated during the acute phase, whereas the majority in the later phase were IFN-stimulated genes. A lack of IFN transcription indicated that this IFN-stimulated gene expression was independent of de novo IFN production. We also observed two groups of genes whose transcription was inhibited by TNF those that resolved toward baseline levels and those that did not. Our study provides insights into the global dynamics of the EC transcriptional response to TNF, highlighting distinct gene expression patterns during the acute and later phases. Data for all coding and noncoding genes is provided on the Web site (http//www.endothelial-response.org/). These findings may be useful in understanding the role of ECs in inflammation and in developing TNF signaling-targeted therapies.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Endotelio Vascular
/
Perfilación de la Expresión Génica
Límite:
Female
/
Humans
/
Male
Idioma:
En
Revista:
J Immunol
Año:
2024
Tipo del documento:
Article
País de afiliación:
Noruega