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Published on: May 2, 2013
PTGS2: A potential immune regulator and therapeutic target for chronic spontaneous urticaria
Yihui Chen1, Xingxing Jian2, Lei Zhu1
1Department of Dermatology, Xiangya Hospital, Central South University, Changsha 410008, China; Hunan Key Laboratory of Skin Cancer and Psoriasis, Xiangya Hospital, Central South University, Changsha 410008, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha 410008, China; Furong Laboratory, Changsha 410008, China.
Aims:
Chronic spontaneous urticaria (CSU) is a common and debilitating skin disease that is difficult to control with existing treatments, and the pathogenesis of CSU has not been fully revealed. The aim of this study was to explore the underlying mechanisms of CSU and identify potential treatments.
Materials And Methods:
Microarray datasets of CSU were obtained from Gene Expression Omnibus database. Differentially expressed genes between skin lesions of CSU and normal controls (LNS-DEGs) were identified, and the enrichment analyses of LNS-DEGs were performed. Hub genes of LNS-DEGs were selected by protein-protein interaction analysis. The co-expression and transcriptional regulatory networks of hub genes were conducted using GeneMANIA and TRRUST database, respectively. CIBERSORT was utilized for immune cell infiltration analysis. Experimental validation was performed by β-hexosaminidase release examination and passive cutaneous anaphylaxis (PCA) mouse model.
Key Findings:
A total of 247 LNS-DEGs were identified, which were enriched in cell migration, cell chemotaxis, and inflammatory pathways such as TNF and interleukin (IL) -17 signaling pathway. Among LNS-DEGs, seven upregulated (PTGS2, CCL2, IL1B, CXCL1, IL6, VCAM1, ICAM1) and one downregulated hub gene (PECAM1) were selected. Immune infiltration analysis identified eight different immune cells, such as activated/resting mast cells and neutrophils. Furthermore, PTGS2, encoding cyclooxygenase 2 (COX2), was selected for further validation. COX2 inhibitor, celecoxib, significantly inhibited mast cell degranulation, and reduced vascular permeability and inflammatory cytokine expression in PCA mouse model.
Significance:
PTGS2 may be a potential regulator of immunity and inflammation in CSU. Targeting PTGS2 is a new perspective for CSU treatment.
Insights
Researchers identified PTGS2 (cyclooxygenase 2) as a key gene in chronic spontaneous urticaria (CSU) pathogenesis. Targeting PTGS2 offers a novel therapeutic strategy for this debilitating skin condition.
Area of Science:
- Immunology
- Dermatology
- Genetics
Background:
- Chronic spontaneous urticaria (CSU) is a prevalent skin disease with unclear pathogenesis and limited treatment options.
- Understanding the molecular mechanisms underlying CSU is crucial for developing effective therapies.
Purpose of the Study:
- To investigate the underlying mechanisms of CSU.
- To identify potential therapeutic targets for CSU.
Main Methods:
- Microarray analysis of CSU skin lesions to identify differentially expressed genes (LNS-DEGs).
- Enrichment analysis, protein-protein interaction, and network analysis to identify hub genes.
- Immune cell infiltration analysis using CIBERSORT.
- Experimental validation using $\beta$-hexosaminidase release assays and a passive cutaneous anaphylaxis (PCA) mouse model.
Main Results:
- 247 LNS-DEGs were identified, enriched in inflammatory pathways like TNF and IL-17 signaling.
- Seven upregulated (PTGS2, CCL2, IL1B, CXCL1, IL6, VCAM1, ICAM1) and one downregulated (PECAM1) hub genes were selected.
- PTGS2 (cyclooxygenase 2) was validated; its inhibitor, celecoxib, reduced mast cell degranulation, vascular permeability, and inflammatory cytokine expression in a PCA mouse model.
Conclusions:
- PTGS2 plays a significant role in regulating immunity and inflammation in CSU.
- Targeting PTGS2 represents a promising new therapeutic approach for CSU treatment.
