期刊
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
卷 146, 期 1, 页码 156-168出版社
MOSBY-ELSEVIER
DOI: 10.1016/j.jaci.2019.12.905
关键词
Atopic dermatitis; IL-32 gamma; miR-205; NF-kappa B
资金
- National Research Foundation of Korea (Republic of Korea) - Korean government [MRC 2017R1A5A2015541, 2018R1A2B2001225]
Background: IL-32 is a novel cytokine involved in many inflammatory diseases. However, the role of IL-32 gamma, an isotype of IL-32, in atopic dermatitis (AD) has not been reported. Objective: We investigated the effects of IL-32 gamma 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-32 gamma transgenic mice. We conducted the therapy experiments by using recombinant IL-32 gamma protein in a reconstructed human skin model and PA-induced model. We conducted a receiver operating characteristic analysis of IL-32 gamma 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-32 gamma transgenic mice compared with in wild-type mice. The concentration of AD-related cytokines was reduced in PA- and MC903-induced IL-32 gamma transgenic mice compared with in wild-type mice. Subsequent analysis showed that IL-32 gamma inhibits miR-205 expression in PA- and MC903-induced skin tissue samples and TNF-alpha/IFN-gamma-treated HaCaT cells. IL-32 gamma reduced NF-kappa B activity in skin tissue samples from PA- and MC903-induced mice and TNF-alpha/IFN-gamma-treated HaCaT cells. NF-kappa B inhibitor treatment with IL-32 gamma expression further suppressed expression of inflammatory mediators as well as miR-205 in TNF-alpha/IFN-gamma-treated HaCaT cells. Furthermore, recombinant IL-32 gamma protein alleviated AD-like inflammation in in vivo and reconstructed human skin models. Spearman correlation analysis showed that serum levels of IL-32 gamma and miR-205 were significantly concordant in patients with AD. Conclusion: Our results indicate that IL-32 gamma reduces AD through the inhibition of miR-205 expression via inactivation of NF-kappa B.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据