학술논문
Anti-chitinase-3-like 1 antibody attenuated atopic dermatitis-like skin inflammation through inhibition of STAT3-dependent CXCL8 expression.
Document Type
Academic Journal
Author
Yu JE; College of Pharmacy and Medical Research Center, Chungbuk National University, Cheongju-si, Chungbuk, Republic of Korea.; College of Pharmacy, Mokpo National University, Muan-gun, Jeonnam, Republic of Korea.; Jeon SH; College of Pharmacy and Medical Research Center, Chungbuk National University, Cheongju-si, Chungbuk, Republic of Korea.; Kim MJ; College of Pharmacy and Medical Research Center, Chungbuk National University, Cheongju-si, Chungbuk, Republic of Korea.; Kim DH; College of Pharmacy and Medical Research Center, Chungbuk National University, Cheongju-si, Chungbuk, Republic of Korea.; Koo JK; College of Pharmacy and Medical Research Center, Chungbuk National University, Cheongju-si, Chungbuk, Republic of Korea.; Kim TH; Autotelic Bio Inc., Cheongju-si, Chungbuk, Republic of Korea.; Kim B; Senelix Co. Ltd., Songpa-gu, Seoul, Republic of Korea.; Yoon JY; PRESTI GEBIOLOGICS Co. Ltd., Cheongju-si, Chungbuk, Republic of Korea.; Lim YS; PRESTI GEBIOLOGICS Co. Ltd., Cheongju-si, Chungbuk, Republic of Korea.; Park SR; New Drug Development Center, Osong Medical Innovation Foundation, Cheongju-si, Chungcheongbuk-do, Korea.; Yeo IJ; College of Pharmacy and Medical Research Center, Chungbuk National University, Cheongju-si, Chungbuk, Republic of Korea.; College of Pharmacy, Kyungpook National University, Buk-gu, Daegu, Republic of Korea.; Yun J; College of Pharmacy and Medical Research Center, Chungbuk National University, Cheongju-si, Chungbuk, Republic of Korea.; Son DJ; College of Pharmacy and Medical Research Center, Chungbuk National University, Cheongju-si, Chungbuk, Republic of Korea.; Han SB; College of Pharmacy and Medical Research Center, Chungbuk National University, Cheongju-si, Chungbuk, Republic of Korea.; Lee YS; College of Pharmacy and Medical Research Center, Chungbuk National University, Cheongju-si, Chungbuk, Republic of Korea.; Hong JT; College of Pharmacy and Medical Research Center, Chungbuk National University, Cheongju-si, Chungbuk, Republic of Korea.
Source
Publisher: Wiley Country of Publication: England NLM ID: 7502536 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1476-5381 (Electronic) Linking ISSN: 00071188 NLM ISO Abbreviation: Br J Pharmacol Subsets: MEDLINE
Subject
Language
English
Abstract
Background and Purpose: Chitinase-3-like 1 (CHI3L1) causes skin inflammation in the progression of atopic dermatitis. We investigated if anti-CHI3L1 antibody could prevent the development of atopic dermatitis and its mechanisms of action.
Experimental Approach: The effect of CHI3L1 antibody on phthalic anhydride-induced atopic dermatitis animal model and in vitro reconstructed human skin (RHS) model were investigated. Expression and release of atopic dermatitis-related cytokines were determined using an enzyme-linked immunosorbent assay, and RT-qPCR, STAT3 and CXCL8 signalling were measured by western blotting.
Key Results: Anti-CHI3L1 antibody suppressed phthalic anhydride-induced epidermal thickening, clinical score, IgE level and infiltration of inflammatory cells, and reduced phthalic anhydride-induced inflammatory cytokines concentration. In addition, CHI3L1 antibody treatment inhibited the expression of STAT3 activity in phthalic anhydride-treated skin. It was also confirmed that CHI3L1 antibody treatment alleviated atopic dermatitis-related inflammation in the RHS model. The inhibitory effects of CHI3L1 antibody was similar or more effective compared with that of the IL-4 antibody. We further found that CHI3L1 is associated with CXCL8 by protein-association network analysis. siRNA of CHI3L1 blocked the mRNA levels of CHI3L1, IL-1β, IL-4, CXCL8, TSLP, and the expression of CHI3L1 and p-STAT, and the level of CXCL8, whereas recombinant level of CXCL8 was elevated. Moreover, siRNA of STAT3 reduced the mRNA level of these cytokines. CHI3L1 and p-STAT3 expression correlated with the reduced CXCL8 level in the RHS in vitro model.
Conclusion and Implications: Our data demonstrated that CHI3L1 antibody could be a promising effective therapeutic drug for atopic dermatitis.
(© 2024 British Pharmacological Society.)
Experimental Approach: The effect of CHI3L1 antibody on phthalic anhydride-induced atopic dermatitis animal model and in vitro reconstructed human skin (RHS) model were investigated. Expression and release of atopic dermatitis-related cytokines were determined using an enzyme-linked immunosorbent assay, and RT-qPCR, STAT3 and CXCL8 signalling were measured by western blotting.
Key Results: Anti-CHI3L1 antibody suppressed phthalic anhydride-induced epidermal thickening, clinical score, IgE level and infiltration of inflammatory cells, and reduced phthalic anhydride-induced inflammatory cytokines concentration. In addition, CHI3L1 antibody treatment inhibited the expression of STAT3 activity in phthalic anhydride-treated skin. It was also confirmed that CHI3L1 antibody treatment alleviated atopic dermatitis-related inflammation in the RHS model. The inhibitory effects of CHI3L1 antibody was similar or more effective compared with that of the IL-4 antibody. We further found that CHI3L1 is associated with CXCL8 by protein-association network analysis. siRNA of CHI3L1 blocked the mRNA levels of CHI3L1, IL-1β, IL-4, CXCL8, TSLP, and the expression of CHI3L1 and p-STAT, and the level of CXCL8, whereas recombinant level of CXCL8 was elevated. Moreover, siRNA of STAT3 reduced the mRNA level of these cytokines. CHI3L1 and p-STAT3 expression correlated with the reduced CXCL8 level in the RHS in vitro model.
Conclusion and Implications: Our data demonstrated that CHI3L1 antibody could be a promising effective therapeutic drug for atopic dermatitis.
(© 2024 British Pharmacological Society.)