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Updated: Jun 18, 2026
08:45
Separation of Rat Epidermis and Dermis with Thermolysin to Detect Site-Specific Inflammatory mRNA and Protein
Published on: September 29, 2021
TNFalpha shedding and epidermal inflammation are controlled by Jun proteins
Juan Guinea-Viniegra1, Rainer Zenz, Harald Scheuch
1Cancer Cell Biology Programme, Centro Nacional de Investigaciones, Oncológicas (CNIO), E-28029 Madrid, Spain.
Genes & Development
|November 26, 2009
Summary
Jun proteins regulate skin inflammation by controlling TNFalpha shedding via the TIMP-3/TACE pathway. Loss of Jun proteins leads to psoriasis-like disease and metabolic cachexia, highlighting a novel therapeutic target.
Area of Science:
- Dermatology
- Molecular Biology
- Immunology
Background:
- Psoriasis is a chronic inflammatory skin disease.
- Tumor Necrosis Factor-alpha (TNFalpha) is a key proinflammatory cytokine implicated in skin inflammation.
- The role of Jun proteins in regulating TNFalpha shedding in the epidermis is not fully understood.
Purpose of the Study:
- To elucidate the molecular mechanism by which Jun proteins regulate TNFalpha shedding in the epidermis.
- To investigate the role of the TIMP-3/TACE pathway in Jun protein-mediated skin inflammation.
- To identify potential therapeutic targets for TNFalpha-associated skin pathologies.
Main Methods:
- Inducible epidermal deletion of JunB and c-Jun in adult mice.
- Genetic mouse models to study the TIMP-3/TACE pathway.
- Analysis of TNFalpha shedding, cytokine cascades, and metabolic parameters.
Main Results:
- Loss of JunB and c-Jun in the epidermis induced a psoriasis-like inflammatory skin disease.
- Jun proteins transcriptionally activate Tissue Inhibitor of Metalloproteinase-3 (TIMP-3), an inhibitor of TNFalpha-Converting Enzyme (TACE).
- Down-regulation of TIMP-3 and increased TACE activity led to excessive TNFalpha shedding, initiating a cytokine cascade and metabolic cachexia.
Conclusions:
- Jun proteins are essential regulators of TNFalpha shedding through the TIMP-3/TACE pathway in the epidermis.
- This pathway is critical for preventing skin inflammation and metabolic exhaustion.
- Targeting the Jun protein-TIMP-3-TACE axis offers a novel therapeutic strategy for inflammatory skin diseases driven by TNFalpha.
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