Abstract
BackgroundChronic autoimmune urticaria (CAU) is a common skin disease and remains unclear understanding of pathogenesis in the vast majority of cases. In order to explore a new therapy for CAU, the current study was performed to investigate the possible functioning of the Oncostatin M receptor (OSMR) gene in the autoimmunity of CAU via regulation of the JAK/STAT3 signaling pathway.MethodsCAU skin tissues from 24 CAU patients and normal skin tissues from normal subjects were collected. Hematoxylin-eosin (HE) staining was conducted to count eosinophils, and immunohistochemistry was carried out to detect the positive rate of OSMR expression in two kinds of skin tissues. A total of 72 Kunming (KM) mice were selected, and 60 mice were used for establishing CAU models and later transfected with different plasmids. The expression of inflammatory factors was evaluated by enzyme-linked immunosorbent assays (ELISA). Expressions of janus kinase (JAK), signal transducer and activator of transcription 3 (STAT3), interferon-stimulated gene 15 (ISG15), CT10-regulated kinase (CRK), and interferon regulatory factor 9 (IRF9) were identified using Western blot assay and reverse transcription quantitative polymerase chain reaction (RT-qPCR). Epithelial cell proliferation was assessed by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide (MTT) assay, and cell cycle distribution and cell apoptosis were assessed using flow cytometry.ResultsThe findings confirm that OSMR protein expression and histamine release rate are highly elevated in human CAU skin tissues, and the expression of the JAK/STAT3 signaling pathway-related genes (OSMR, JAK2, STAT3, ISG15, CRK and IRF9) was up-regulated. OSMR gene silencing in CAU mice significantly decreases the content of inflammatory factors (IL-1, IL-6, IFN-γ, and IgE), the number of eosinophils, and reduces the expression of the JAK/STAT3 signaling pathway related genes, and further enhances cell proliferation, promotes cell cycle entry and inhibits apoptosis of epithelial cells.ConclusionAll aforementioned results indicate that OSMR gene silencing inhibits the activation of the JAK/STAT3 signaling pathway, thereby suppressing the development of CAU.
Highlights
Chronic autoimmune urticaria (CAU) is a common skin disease and remains unclear understanding of pathogenesis in the vast majority of cases
Higher Oncostatin M receptor (OSMR) positive expression rate and elevated expression of the janus kinase (JAK)/signal transducer and activator of transcription 3 (STAT3) signaling pathway-related genes in CAU skin tissues In order to better investigate the expression of OSMR in CAU skin tissues, CAU and normal skin tissues were observed under the light microscope
The findings indicate that OSMR positive cells were primarily located in the superficial and middle dermis, surrounding the blood vessels and appendages in CAU skin tissues, with the positive granule largely located inside the epithelial cells
Summary
Chronic autoimmune urticaria (CAU) is a common skin disease and remains unclear understanding of pathogenesis in the vast majority of cases. Chronic idiopathic urticaria (CIU) is a common type of CU accounting for over 70% cases of CU, and chronic autoimmune urticaria (CAU), a subgroup of CIU, accounts for more than 30% of CIU. Clinical suspicion and autologous serum skin test (ASST) are regarded as the basis of CAU diagnosis (Abd El-Azim & Abd, 2011). The role of omalizumab in treating refractory CAU patients was studied, and proven possible (Al-Ahmad, 2010). Mizoribine was found to be an effective therapy in some CAU patients, and may possibly be effective for patients not responsive to traditional therapy (Hashimoto et al, 2012). New genetic methods are required to find the possible ways for the treatment of CAU
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