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Updated: Jun 19, 2026
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NF-κB-dependent Luciferase Activation and Quantification of Gene Expression in Salmonella Infected Tissue Culture Cells
Published on: January 12, 2020
A teleost-specific oxygen-immunity axis where FIH activates NF-κB via competitive IκBα binding
Zhipeng Zhan1,2, Mincong Liang1,2, Yang Yu2
1School of Life Sciences, China-Association of Southeast Asian Nations (ASEAN) Belt and Road Joint Laboratory on Mariculture Technology and State Key Laboratory for Biocontrol, Guangdong Province Key Laboratory for Aquatic Economic Animals, Sun Yat-sen University, Guangzhou 510275, China.
Summary
A novel oxygen-immunity axis in teleosts links the factor inhibiting HIF (FIH) to NF-κB activation, crucial for innate immunity during aquatic hypoxia. This hydroxylase-independent mechanism has evolutionary and aquaculture health implications.
Area of Science:
- Immunology
- Environmental Science
- Molecular Biology
Background:
- Aquatic deoxygenation due to global warming challenges teleost immune systems.
- Molecular mechanisms balancing metabolic adaptation and pathogen resistance under hypoxia are poorly understood.
Purpose of the Study:
- To identify the molecular axis regulating oxygen sensing and innate immunity in teleosts.
- To investigate the role of the oxygen sensor FIH in the NF-κB pathway under hypoxic conditions.
Main Methods:
- Utilized FIH mutants and knockdown experiments in teleosts.
- Employed CRISPR/Cas9 gene editing in zebrafish (drfih-/-).
- Performed in vitro binding assays, AlphaFold3 modeling, and cross-species analyses.
Main Results:
- FIH activates NF-κB by competitively displacing p65 from IκBα, independent of FIH hydroxylase activity.
- FIH knockdown and drfih-/- zebrafish exhibit reduced NF-κB-driven inflammation and altered immune responses.
- A conserved competitive interface for FIH-IκBα binding is present in aquatic vertebrates but not terrestrial species.
Conclusions:
- Discovered a hydroxylase-independent oxygen-immunity regulatory axis in teleosts involving FIH and NF-κB.
- This mechanism is lineage-specific to aquatic vertebrates and impacts innate immunity under hypoxia.
- Findings are relevant to vertebrate evolution, climate change adaptation, and aquaculture health.
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