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牛磺胆酸钠口服给药,一种 GPCR19 激动剂,可有效改善小鼠模型中的特应性皮炎。

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

机构信息

Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Korea.

Wide River Institute of Immunology, Seoul National University, Seoul, South Korea.

出版信息

Exp Dermatol. 2024 Oct;33(10):1-7. doi: 10.1111/exd.15193.

Abstract

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.

摘要

特应性皮炎(AD)是最常见的慢性炎症性皮肤疾病,其特征为剧烈瘙痒和反复出现的湿疹样损伤。最近,美国食品药品监督管理局(FDA)已批准使用 Janus 激酶(JAK)抑制剂治疗 AD 患者。然而,口服免疫调节剂已被证明存在不良反应。在之前的研究中,我们证明了牛磺胆酸钠(TDCA)作为一种 G 蛋白偶联受体 19(GPCR19)激动剂治疗 AD 的疗效。在这项研究中,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 显著改善了 AD 症状,并减少了表皮和真皮的厚度。此外,口服 TDCA 治疗抑制了髓样和淋巴样细胞浸润 AD 病变。TDCA 还抑制了皮肤和血液中胸腺基质淋巴细胞生成素(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 基元)配体 17 的表达。鉴于 TDCA 先前表现出的安全性特征,口服 TDCA 可能为 AD 患者提供一种有益且更安全的选择。

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