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

Yong Sun Lee, Sang-Bae Han, Hyeon Joo Ham, Ju Ho Park, Jong Sung Lee, Dae Yeon Hwang, Young Suk Jung, Do Young Yoon, Jin Tae Hong

The Journal of allergy and clinical immunology 2020 Jul

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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. We investigated the effects of IL-32γ on development of AD and its action mechanisms. 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. 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. Our results indicate that IL-32γ reduces AD through the inhibition of miR-205 expression via inactivation of NF-κB. Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.

Citation

Yong Sun Lee, Sang-Bae Han, Hyeon Joo Ham, Ju Ho Park, Jong Sung Lee, Dae Yeon Hwang, Young Suk Jung, Do Young Yoon, Jin Tae Hong. IL-32γ suppressed atopic dermatitis through inhibition of miR-205 expression via inactivation of nuclear factor-kappa B. The Journal of allergy and clinical immunology. 2020 Jul;146(1):156-168