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Nuclear factor-kappaB regulates the transcription of NADPH oxidase 1 in human alveolar epithelial cells
- Source :
- BMC Pulmonary Medicine, Vol 21, Iss 1, Pp 1-12 (2021), BMC Pulmonary Medicine
- Publication Year :
- 2021
- Publisher :
- BMC, 2021.
-
Abstract
- Objective Acute lung injury (ALI) is characterized by inflammation and oxidative stress. Nuclear factor-kappaB (NF-κB) mediates the expression of various inflammation-related genes, including the NADPH oxidase family. This study aimed to identify the potential regulatory role of NF-κB on NADPH oxidases in tumor necrosis factor-α (TNF-α)-induced oxidative stress in human alveolar epithelial cells. Methods A549 cells were treated with TNF-α for 24 h to establish ALI cell models. RT-PCR, western blot, assessment of oxidative stress, Alibaba 2.1 online analysis, electrophoretic mobility shift assays and luciferase reporter analysis were employed to identify the potential regulatory role of NF-κB on NADPH oxidases in TNF-α-induced oxidative stress in human alveolar epithelial cells. Results The expression of NF-κB/p65 was notably upregulated in TNF-α-stimulated A549 cells. NF-κB knockdown by siRNA significantly inhibited the TNF-α-induced oxidative stress. Moreover, NF-κB/p65 siRNA could inhibit the activation of NOX1, NOX2 and NOX4 mRNA and protein expression in TNF-α-stimulated A549 cells. The next study demonstrated that NF-κB activated the transcription of NOX1 by binding to the -261 to -252 bp (NOX1/κB2, TAAAAATCCC) region of NOX1 promoter in TNF-α-stimulated A549 cells. Conclusion Our data demonstrated that NF-κB can aggravate TNF-α-induced ALI by regulating the oxidative stress response and the expression of NOX1, NOX2 and NOX4. Moreover, NF-κB could promote the NOX1 transcriptional activity via binding its promoter in TNF-α-stimulated A549 cells.
- Subjects :
- Pulmonary and Respiratory Medicine
Transcription, Genetic
Lung injury
medicine.disease_cause
Gene Expression Regulation, Enzymologic
03 medical and health sciences
0302 clinical medicine
NOX1
Acute lung injury
Medicine
Humans
Cells, Cultured
030304 developmental biology
A549 cell
Inflammation
lcsh:RC705-779
0303 health sciences
NADPH oxidase
biology
business.industry
Tumor Necrosis Factor-alpha
NF-kappa B
NOX4
NADPH Oxidase 1
NADPH Oxidases
lcsh:Diseases of the respiratory system
Cell biology
Up-Regulation
Tumor necrosis factor-α
Oxidative Stress
A549 Cells
030220 oncology & carcinogenesis
Alveolar Epithelial Cells
biology.protein
cardiovascular system
Tumor necrosis factor alpha
Nuclear factor-kappaB
business
Reactive oxygen species
Oxidative stress
Research Article
Subjects
Details
- Language :
- English
- ISSN :
- 14712466
- Volume :
- 21
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- BMC Pulmonary Medicine
- Accession number :
- edsair.doi.dedup.....7a0c451f1297b078c2d9d59f4a6f2c35