Abstract
CD93 has been shown critical roles in inflammatory and immune diseases. However, in allergic asthma, the potential roles of soluble CD93 (sCD93) have not been well studied. We conducted house dust mite (HDM) stimulation with Der p 1 in BEAS-2B and U937 cells, followed by treatment with dexamethasone or small interfering RNA against CD93. A HDM-induced murine allergic asthma model was also established. We estimated the power of sCD93 to predict allergic asthma in a retrospective post-hoc analysis containing 96 human samples. HDM-stimulated BEAS-2B cells showed increased mRNA expression levels of IL-6, IL-8, IL-33, TSLP, and CD93. The CD93 level in culture supernatants steadily increased for 24 h after allergen stimulation, which was significantly suppressed by both dexamethasone and CD93 silencing. CD93 silencing increased IL-6 and TSLP, but not IL-33 levels in culture supernatants. HDM-induced asthma mice showed significant airway hyperresponsiveness and inflammation with Th2 cytokine activation, along with decreased CD93 expression in bronchial epithelial cells and lung homogenates but increased serum CD93 levels. The sCD93 level in asthma patients was significantly higher than that in healthy controls and could predict asthma diagnosis with moderate sensitivity (71.4%) and specificity (82.4%) (AUC = 0.787, P < 0.001). The level of sCD93 which has potential role to predict asthma significantly increased after HDM stimulation via IL-6 and TSLP in vitro and in vivo.
Highlights
CD93 has been shown critical roles in inflammatory and immune diseases
The mRNA expression of IL-6, IL-8, IL-33, thymic stromal lymphopoietin (TSLP), and CD93 was steadily increased according to the increase of Der p 1 concentration. (Fig. 2A–E)
The mRNA expression levels of TSLP, IL-33, and CD93 significantly increased after 1 h and sharply decreased to the baseline level at 2 and 4 h after house dust mite (HDM) treatment (Fig. 2F–H)
Summary
CD93 has been shown critical roles in inflammatory and immune diseases. in allergic asthma, the potential roles of soluble CD93 (sCD93) have not been well studied. The level of sCD93 which has potential role to predict asthma significantly increased after HDM stimulation via IL-6 and TSLP in vitro and in vivo. Raedler et al.[12] showed that CD93 gene expression was significantly higher in non-allergic asthma patients than healthy controls, and Sigari et al.[13] demonstrated that the serum CD93 level increased under asthma exacerbation and decreased following proper treatment. The changes of sCD93 after allergic stimulation have not been assessed in vitro, and the potential of sCD93 as a biomarker to help in asthma diagnosis remains unknown Toward this end, the aim of this study was to assess the roles of sCD93 in allergic inflammation using in vitro and in vivo analysis with cell and murine models induced using house dust mite (HDM) extract. Since the serum sCD93 level can be obtained and interpreted objectively, clarifying the potential role of serum CD93 in asthma patients would provide a valuable tool for clinical diagnosis and management
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