The Journal of allergy and clinical immunology, 2020.146(1), 156-168, DOI: https://doi.org/10.1016/j.jaci.2019.12.905

IL-32γ suppressed atopic dermatitis through inhibition of miR-205 expression via inactivation of nuclear factor-kappa B

Lee YS, Han SB;Ham HJ;Park JH;Lee JS;Hwang DY;Jung YS;Yoon DY;Hong JT

Abstract

Background: IL-32 is a novel cytokine involved in many inflammatory diseases. However, the role of IL-32g, an isotype of IL-32, in atopic dermatitis (AD) has not been reported.
Objective: We investigated the effects of IL-32g 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-32g transgenic mice. We conducted the therapy experiments by using recombinant IL-32g protein in a reconstructed human skin model and PA-induced model. We conducted a receiver operating characteristic analysis of IL-32g 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-32g transgenic mice compared with in wild-type mice. The concentration of AD-related cytokines was reduced in PA- and MC903-induced IL-32g transgenic mice compared with in wild-type mice. Subsequent analysis showed that IL-32g inhibits miR-205 expression in PA- and MC903-induced skin tissue samples and TNF-a/IFN-g–treated HaCaT cells. IL-32g reduced NF-kB activity in skin tissue samples from PA- and MC903-induced mice and TNF-a/IFN-g–treated HaCaT cells.
NF-kB inhibitor treatment with IL-32g expression further suppressed expression of inflammatory mediators as well as miR-205 in TNF-a/IFN-g–treated HaCaT cells. Furthermore, recombinant IL-32g protein alleviated AD-like inflammation in in vivo and reconstructed human skin models. Spearman correlation analysis showed that serum levels of IL-32g and miR-205 were significantly concordant in patients with AD.
Conclusion: Our results indicate that IL-32g reduces AD through the inhibition of miR-205 expression via inactivation of NF-kB.

• DOI: https://doi.org/10.1016/j.jaci.2019.12.905
• ISBN or ISSN: 0091-6749

• 본 연구는 질병관리본부 연구개발과제연구비를 지원받아 수행되었습니다.
• This research was supported by a fund by Research of Korea Centers for Disease Control and Prevention.