%0 Journal Article
%T PTGS2: A potential immune regulator and therapeutic target for chronic spontaneous urticaria.
%A Chen Y
%A Jian X
%A Zhu L
%A Yu P
%A Yi X
%A Cao Q
%A Wang J
%A Xiong F
%A Li J
%J Life Sci
%V 344
%N 0
%D 2024 May 1
%M 38514006
%F 6.78
%R 10.1016/j.lfs.2024.122582
%X OBJECTIVE: 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.
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.
RESULTS: 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.
CONCLUSIONS: PTGS2 may be a potential regulator of immunity and inflammation in CSU. Targeting PTGS2 is a new perspective for CSU treatment.