Background

IL-32 is a novel cytokine involved in many inflammatory diseases. However, the role of IL-32γ, an isotype of IL-32, in atopic dermatitis (AD) has not been reported.

Objective

We investigated the effects of IL-32γ on development of AD and its action mechanisms.

Methods

We used phthalic anhydride (PA) and an MC903-induced AD model using wild-type and IL-32γ transgenic mice. We conducted the therapy experiments by using recombinant IL-32γ protein in a reconstructed human skin model and PA-induced model. We conducted a receiver operating characteristic analysis of IL-32γ with new AD biomarkers, IL-31 and IL-33, in serum from patients with AD.

Results

Dermatitis severity and epidermal thickness were significantly reduced in PA- and MC903-induced IL-32γ transgenic mice compared with in wild-type mice. The concentration of AD-related cytokines was reduced in PA- and MC903-induced IL-32γ transgenic mice compared with in wild-type mice. Subsequent analysis showed that IL-32γ inhibits miR-205 expression in PA- and MC903-induced skin tissue samples and TNF-α/IFN-γ–treated HaCaT cells. IL-32γ reduced NF-κB activity in skin tissue samples from PA- and MC903-induced mice and TNF-α/IFN-γ–treated HaCaT cells. NF-κB inhibitor treatment with IL-32γ expression further suppressed expression of inflammatory mediators as well as miR-205 in TNF-α/IFN-γ–treated HaCaT cells. Furthermore, recombinant IL-32γ protein alleviated AD-like inflammation in in vivo and reconstructed human skin models. Spearman correlation analysis showed that serum levels of IL-32γ and miR-205 were significantly concordant in patients with AD.

Conclusion

Our results indicate that IL-32γ reduces AD through the inhibition of miR-205 expression via inactivation of NF-κB.

中文翻译：

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IL-32γ通过灭活核因子-κB抑制miR-205表达来抑制特应性皮炎。

背景

IL-32是一种涉及许多炎性疾病的新型细胞因子。然而，尚未报道IL-32的同种型IL-32γ在特应性皮炎（AD）中的作用。

目的

我们调查了IL-32γ对AD的发展及其作用机制的影响。

方法

我们使用邻苯二甲酸酐（PA）和使用野生型和IL-32γ转基因小鼠的MC903诱导的AD模型。我们通过在重组的人皮肤模型和PA诱导的模型中使用重组IL-32γ蛋白进行了治疗实验。我们对来自AD患者血清中的带有新AD生物标志物IL-31和IL-33的IL-32γ进行了受体工作特征分析。

结果

与野生型小鼠相比，PA和MC903诱导的IL-32γ转基因小鼠的皮肤炎严重程度和表皮厚度显着降低。与野生型小鼠相比，PA和MC903诱导的IL-32γ转基因小鼠中AD相关细胞因子的浓度降低。随后的分析表明，IL-32γ抑制了PA和MC903诱导的皮肤组织样品以及TNF-α/IFN-γ处理的HaCaT细胞中miR-205的表达。IL-32γ降低了PA和MC903诱导的小鼠以及TNF-α/IFN-γ处理的HaCaT细胞的皮肤组织样本中的NF-κB活性。用IL-32γ表达的NF-κB抑制剂处理进一步抑制了TNF-α/IFN-γ处理的HaCaT细胞中炎性介质以及miR-205的表达。此外，重组IL-32γ蛋白可减轻体内AD样炎症并重建人类皮肤模型。Spearman相关分析显示，AD患者的血清IL-32γ和miR-205水平显着一致。

结论

我们的结果表明，IL-32γ通过抑制NF-κB的表达来抑制miR-205的表达，从而降低AD。