Pharmacologic inhibition of Il6st/gp130 improves dermatological inflammation and pruritus.

Autor: Kim M; Department of Biomedical Sciences, Korea University College of Medicine, Seoul 02841, Republic of Korea., Kim C; Department of Biomedical Sciences, Korea University College of Medicine, Seoul 02841, Republic of Korea., Zheng H; Department of Biomedical Sciences, Korea University College of Medicine, Seoul 02841, Republic of Korea., Kim Y; Department of Biomedical Sciences, Korea University College of Medicine, Seoul 02841, Republic of Korea., Cho PS; Department of Biomedical Sciences, Korea University College of Medicine, Seoul 02841, Republic of Korea., Lim JY; Department of Biomedical Sciences, Korea University College of Medicine, Seoul 02841, Republic of Korea., Choi W; Korea University Guro Hospital, Seoul 08308, Republic of​ Korea., Kim M; Department of Biomedical Sciences, Korea University College of Medicine, Seoul 02841, Republic of Korea., Kim Y; Department of Biomedical Sciences, Korea University College of Medicine, Seoul 02841, Republic of Korea., Kim HR; Department of Biomedical Sciences, Korea University College of Medicine, Seoul 02841, Republic of Korea., Lee GY; Department of Microbiology & Immunology, Cornell University, Ithaca, New York, NY 14853, USA., Hwang SW; Department of Biomedical Sciences, Korea University College of Medicine, Seoul 02841, Republic of Korea; Department of Physiology, Korea University College of Medicine, Seoul 02841, Republic of Korea. Electronic address: sunhwang@korea.ac.kr.
Jazyk: angličtina
Zdroj: Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie [Biomed Pharmacother] 2024 Sep; Vol. 178, pp. 117155. Date of Electronic Publication: 2024 Jul 23.
DOI: 10.1016/j.biopha.2024.117155
Abstrakt: Chronic dermatitis is a disease with large unmet need for pharmacological improvement. Dermatitis conditions are maintained and exacerbated by various cytokine actions in the context of inflammation. Interleukin 6 signal transducer (Il6st), also known as glycoprotein 130 (Gp130), is a key component for surface reception of a multitude of cytokines and transduction and amplification of their pro-inflammatory signals. We hypothesized accordingly that pharmacological inhibition of Il6st can alter dermatitis pathology. Treatment with SC-144 and bazedoxifene, two representative small molecule Il6st inhibitors with different binding modes led to moderate but significant improvement of skin conditions in a 1-chloro-2,4-dinitrobenzene animal model. Part of cytokine expressions indicating the dermatological index were normalized particularly when treated with SC-144. Pruritic behaviors were blunted, also possibly giving limited contribution to disease improvement. In psoriatic skin and itch of an imiquimod animal model, those two treatments appeared to be relatively moderate. Collectively, pharmacological inhibition of Il6st seems to lessen pathological irritation. Inversely, this experimental attempt newly implies that Il6st participates in pathological mechanisms. In conclusion, we suggest Il6st as a novel target for improving dermatitis, and that agents with suitable efficacy and safety for its modulation are translatable.
Competing Interests: Declaration of Competing Interest The authors declare that there is no conflict of interest regarding the publication of this article.
(Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)
Databáze: MEDLINE
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