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Published on: August 25, 2017
Hyperoxia synergistically increases TNF-alpha-induced interleukin-8 gene expression in A549 cells
G L Allen1, I Y Menendez, M A Ryan
1Division of Critical Care Medicine, Children's Hospital Research Foundation, Cincinnati, Ohio 45229, USA.
Summary
Hyperoxia alone minimally affects Interleukin-8 (IL-8) gene expression. However, combined with tumor necrosis factor-alpha (TNF-alpha), hyperoxia synergistically boosts IL-8 production via NF-kappaB and NF-IL-6 pathways.
Area of Science:
- Respiratory Medicine
- Molecular Biology
- Immunology
Background:
- Interleukin-8 (IL-8) is a key mediator in acute lung injury.
- The impact of hyperoxia on IL-8 gene expression in respiratory epithelium is not fully understood.
- The combined effects of hyperoxia and proinflammatory cytokines on IL-8 expression require further characterization.
Purpose of the Study:
- To investigate the effect of hyperoxia alone and in combination with TNF-alpha on IL-8 gene expression in respiratory epithelial cells.
- To elucidate the molecular mechanisms underlying the synergistic IL-8 gene expression induced by hyperoxia and TNF-alpha.
Main Methods:
- Cultured A549 respiratory epithelial cells were treated with hyperoxia, TNF-alpha, or both.
- IL-8 gene expression was quantified using ELISA and Northern blot analyses.
- Molecular mechanisms were explored via IL-8 promoter-reporter assays, electrophoretic mobility shift assays (EMSA), and Western blot analyses.
Main Results:
- Hyperoxia alone had a minimal effect on IL-8 gene expression.
- TNF-alpha alone increased IL-8 gene expression in a time-dependent manner.
- The combination of hyperoxia and TNF-alpha synergistically increased IL-8 gene expression, involving augmented NF-kappaB activation and prolonged nuclear translocation, with additional requirement for the NF-IL-6 site.
Conclusions:
- Hyperoxia alone has a limited impact on IL-8 gene expression in respiratory epithelial cells.
- Hyperoxia synergistically enhances TNF-alpha-induced IL-8 gene expression.
- This synergistic effect is mediated by the cooperative interaction of transcription factors NF-kappaB and NF-IL-6.
