口服 GPCR19 激动剂 Taurodeoxycholate 能有效缓解小鼠模型中的特应性皮炎

IF 3.5 3区 医学 Q1 DERMATOLOGY Experimental Dermatology Pub Date : 2024-10-21 DOI:10.1111/exd.15193
Aziz Ghaderpour, Ju-Young Jeong, Young-Jae Koh, Seung-Yong Seong
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引用次数: 0

摘要

特应性皮炎(AD)是最常见的慢性炎症性皮肤病,以剧烈瘙痒和反复发作的湿疹性皮损为特征。最近,美国 FDA 批准了 Janus 激酶(JAK)抑制剂用于 AD 患者的口服治疗。然而,口服免疫调节剂也有不良反应。在之前的研究中,我们证实了外用 G 蛋白偶联受体 19(GPCR19)激动剂牛磺脱氧胆酸盐(TDCA)对 AD 的疗效。在本研究中,我们进一步评估了口服 TDCA 对 MC903 和二硝基氯苯(DNCB)诱导的 AD 小鼠模型的疗效。口服 TDCA 能明显改善 AD 症状,减少表皮和真皮厚度。此外,口服 TDCA 还能抑制髓系细胞和淋巴细胞向 AD 病灶的浸润。TDCA 还能抑制皮肤和血液中胸腺基质淋巴生成素 (TSLP)、白细胞介素 (IL)-4、IL-13、IL-33、IL-1β、肿瘤坏死因子-α (TNF-α) 和趋化因子 (C-C motif) 配体 17 的表达。鉴于 TDCA 先前已证实的安全性,口服 TDCA 可能会为注意力缺失症患者提供一种有益且更安全的替代疗法。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

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Oral Administration of Taurodeoxycholate, A GPCR19 Agonist, Effectively Ameliorates Atopic Dermatitis in A Mouse Model

Atopic dermatitis (AD) is the most prevalent chronic inflammatory skin disorder, characterised by intense pruritus and recurrent eczematous lesions. Recently, the US FDA has approved Janus kinase (JAK) inhibitors for oral treatment in AD patients. However, oral immunomodulatory agents have demonstrated adverse effects. In previous studies, we demonstrated the efficacy of topical taurodeoxycholate (TDCA), a G protein-coupled receptor 19 (GPCR19) agonist, on AD. In this study, we further evaluated the efficacy of orally administered TDCA on MC903- and dinitrochlorobenzene (DNCB)-induced AD mouse models. Oral administration of TDCA significantly ameliorated AD symptoms and reduced both epidermal and dermal thickness. Additionally, oral TDCA treatment inhibited the infiltration of myeloid and lymphoid cells into AD lesions. TDCA also suppressed the expression of thymic stromal lymphopoietin (TSLP), interleukin (IL)-4, IL-13, IL-33, IL-1β, tumour necrosis factor-alpha (TNF-α) and chemokine (C-C motif) ligand 17 in the skin and blood. Given the previously demonstrated safety profiles of TDCA, oral TDCA may offer a beneficial and safer alternative for AD patients.

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来源期刊
Experimental Dermatology
Experimental Dermatology 医学-皮肤病学
CiteScore
6.70
自引率
5.60%
发文量
201
审稿时长
2 months
期刊介绍: Experimental Dermatology provides a vehicle for the rapid publication of innovative and definitive reports, letters to the editor and review articles covering all aspects of experimental dermatology. Preference is given to papers of immediate importance to other investigators, either by virtue of their new methodology, experimental data or new ideas. The essential criteria for publication are clarity, experimental soundness and novelty. Letters to the editor related to published reports may also be accepted, provided that they are short and scientifically relevant to the reports mentioned, in order to provide a continuing forum for discussion. Review articles represent a state-of-the-art overview and are invited by the editors.
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