Yong Sun Lee1, Sang-Bae Han1, Hyeon Joo Ham1, Ju Ho Park1, Jong Sung Lee1, Dae Yeon Hwang2, Young Suk Jung3, Do Young Yoon4, Jin Tae Hong5. 1. College of Pharmacy and Medical Research Center, Chungbuk National University, Chungbuk, Korea. 2. Department of Biomaterial Science, College of Natural Resources and Life Science/Life and Industry Convergence Research Institute, Pusan National University, Miryang, Korea. 3. College of Pharmacy, Pusan National University, Busan, Korea. 4. Department of Bioscience and Biotechnology, Konkuk University, Seoul, Korea. Electronic address: ydy4218@konkuk.ac.kr. 5. College of Pharmacy and Medical Research Center, Chungbuk National University, Chungbuk, Korea. Electronic address: jinthong@chungbuk.ac.kr.
Abstract
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.
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.
Authors: Alin Laurentiu Tatu; Anca Arbune; Valentin Chioncel; Elena Niculet; Thomas Nadasdy; Carmen Bobeica; Alina Viorica Iancu; Caterina Dumitru; Valentin Tudor Popa; Nicolas Kluger; Victor Gabriel Clatici; Claudiu Ionut Vasile; Cristian Onisor; Alexandru Nechifor Journal: J Inflamm Res Date: 2022-09-08