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Published on: June 25, 2015
Peroxiredoxin-6 Negatively Regulates Bactericidal Activity and NF-κB Activity by Interrupting TRAF6-ECSIT Complex
Yoon Min1, Sae M Wi1, Dongwoo Shin1
1Department of Molecular Cell Biology and Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine Suwon, South Korea.
Frontiers in Cellular and Infection Microbiology
|April 11, 2017
Summary
Peroxiredoxin-6 (Prdx6) regulates mitochondrial reactive oxygen species (mROS) and nuclear factor-kappa B (NF-κB) activation by Toll-like receptor 4 (TLR4). Prdx6 inhibits the TRAF6-ECSIT complex, impacting inflammatory responses and bacterial infection resistance.
Area of Science:
- Immunology
- Cell Biology
- Biochemistry
Background:
- Toll-like receptor 4 (TLR4) signaling involves mitochondrial reactive oxygen species (mROS) and nuclear factor-kappa B (NF-κB) activation, mediated by the TRAF6-ECSIT complex.
- Peroxiredoxin-6 (Prdx6) is an antioxidant enzyme involved in cellular signaling pathways.
Purpose of the Study:
- To investigate the regulatory role of Prdx6 in TLR4-induced mROS production and NF-κB activation.
- To elucidate the molecular mechanism by which Prdx6 influences the TRAF6-ECSIT complex and subsequent cellular responses.
Main Methods:
- Utilized Prdx6-knockdown (Prdx6KD) THP-1 cells and TLR4 stimulation.
- Performed biochemical studies to analyze protein interactions, including Prdx6 with TRAF6 and ECSIT.
- Assessed mROS levels, NF-κB activation, pro-inflammatory cytokine production, and bacterial infection resistance.
Main Results:
- TLR4 stimulation induced Prdx6 translocation into mitochondria.
- Prdx6KD cells exhibited increased mROS levels and resistance to Salmonella typhimurium infection.
- Prdx6 competitively inhibited the TRAF6-ECSIT interaction via its C-terminal TRAF-C domain, suppressing NF-κB activation and pro-inflammatory cytokine production.
Conclusions:
- Prdx6 acts as a negative regulator of TLR4 signaling by disrupting the TRAF6-ECSIT complex.
- This disruption leads to reduced mitochondrial ROS production and inhibited NF-κB activation, impacting inflammatory responses and bactericidal activity.
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