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Activation and Measurement of NLRP3 Inflammasome Activity Using IL-1β in Human Monocyte-derived Dendritic Cells
Published on: May 22, 2014
The pattern recognition receptor NOD2 mediates Staphylococcus aureus-induced IL-17C expression in keratinocytes
Sarah A Roth1, Maren Simanski1, Franziska Rademacher1
1Department of Dermatology, University Hospital Schleswig-Holstein, Kiel, Germany.
The Journal of Investigative Dermatology
|July 30, 2013
Summary
Staphylococcus aureus activates nucleotide-binding oligomerization domain-containing protein 2 (NOD2) in skin cells, increasing IL-17C production. This innate immunity pathway may be altered in atopic dermatitis.
Area of Science:
- Immunology
- Microbiology
- Dermatology
Background:
- Interleukin-17C (IL-17C) is a cytokine produced by epithelial cells that enhances innate immunity.
- Nucleotide-binding oligomerization domain-containing protein 2 (NOD2) is a pattern recognition receptor involved in detecting bacterial components.
Purpose of the Study:
- To investigate the role of NOD2 in Staphylococcus aureus-induced IL-17C production in keratinocytes.
- To explore the functional consequences of NOD2 activation and its variants on S. aureus infection and IL-17C expression.
Main Methods:
- HEK293 cells and primary human keratinocytes were used to study IL-17C promoter activity and gene expression.
- NOD2 activation was induced by S. aureus infection, and its role was assessed using overexpression and siRNA knockdown.
- NOD2 variants associated with Crohn's disease and atopic dermatitis were analyzed.
Main Results:
- NOD2 activation in HEK293 cells induced IL-17C promoter activity, which was impaired by Crohn's disease-associated NOD2 mutations.
- S. aureus infection upregulated NOD2 and IL-17C in keratinocytes, with NOD2 overexpression enhancing IL-17C induction.
- NOD2 deficiency reduced S. aureus clearance, while IL-17C knockdown increased bacterial survival.
Conclusions:
- S. aureus activates NOD2 in keratinocytes, leading to increased IL-17C expression and enhanced bacterial clearance.
- Dysregulation of the NOD2-IL-17C axis may contribute to the pathogenesis of atopic dermatitis.
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