한빛사 논문
Yong Sun Lee MSc1,∗, Sang-Bae Han PhD1,∗, Hyeon Joo Ham BSc1, Ju Ho Park MSc1, Jong Sung Lee BSc1, Dae Yeon Hwang PhD2, Young Suk Jung PhD3, Do Young Yoon PhD4, Jin Tae Hong PhD1
1 College of Pharmacy and Medical Research Center, Chungbuk National University, Osongsaengmyeong 1-ro 194-21, Osong-eup, Heungduk-gu, Cheongju, Chungbuk, 28160, Republic of Korea
2 Department of Biomaterial Science, College of Natural Resources and Life Science/Life and Industry Convergence Research Institute, Pusan National University, Miryang 50463, Republic of Korea
3 College of Pharmacy, Pusan National University, Busandaehag-ro, Geumjeong-gu, Busan 46241, Republic of Korea
4 Department of Bioscience and Biotechnology, Konkuk University, Gwangjin-gu, Seoul 05029, Republic of Korea
Correspondence : Do Young Yoon, Jin Tae Hong
*The authors are equally contributed.
Abstract
Background
Interleukin 32 (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 has not been reported.
Objective
We investigated the effects of IL-32γ on the atopic dermatitis development and its action mechanisms.
Methods
We used phthalic anhydride (PA) and MC903-inudced atopic dermatitis model using wild type and IL-32γ transgenic mice. We conducted the therapy experiments using recombinant IL-32γ protein in reconstructed human skin model and PA-induced model. We conducted the receive operating characteristic analysis of IL-32γ with new atopic dermatitis biomarkers, IL-31 and IL-33, in serum from atopic dermatitis patients.
Results
Dermatitis severity and epidermal thickness were significantly reduced in PA and MC903-induced IL-32γ transgenic mice compared to wild type mice. The concentration of AD-related cytokines was reduced in PA and MC903-induced IL-32γ transgenic mice compared to wild type mice. Subsequent analysis showed that IL-32γ inhibits miR-205 expression in PA and MC903-induced skin tissues and TNF-α/IFN-γ-treated HaCaT cells. IL-32γ reduced NF-κB activity in skin tissues 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 atopic dermatitis-like inflammation in in vivo and reconstructed human skin model. Spearman’s correlation analysis showed that serum levels of IL-32γ and miR-205 were significantly concordant in patients with atopic dermatitis.
Conclusion
Our results indicate that IL-32γ reduces atopic dermatitis through the inhibition of miR-205 expression via inactivation of NF-κB.
Key words
Atopic dermatitis; IL-32γ; miR-205; NF-κB
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