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. 2024 Sep;181(17):3232-3245.
doi: 10.1111/bph.16365. Epub 2024 May 14.

Anti-chitinase-3-like 1 antibody attenuated atopic dermatitis-like skin inflammation through inhibition of STAT3-dependent CXCL8 expression

Ji Eun Yu  1   2 , Seong Hee Jeon  1 , Min Ji Kim  1 , Dae Hwan Kim  1 , Ja Keun Koo  1 , Tae Hun Kim  3 , Bongcheol Kim  4 , Ji Yong Yoon  5 , Young-Soo Lim  5 , So Ra Park  6 , In Jun Yeo  1   7 , Jaesuk Yun  1 , Dong Ju Son  1 , Sang-Bae Han  1 , Yong Sun Lee  1 , Jin Tae Hong  1
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Free article

Anti-chitinase-3-like 1 antibody attenuated atopic dermatitis-like skin inflammation through inhibition of STAT3-dependent CXCL8 expression

Ji Eun Yu et al. Br J Pharmacol. 2024 Sep.
Free article

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.

Keywords: CHI3L1; CHI3L1 antibody; CXCL8; STAT3; atopic dermatitis.

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References

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