Department of Immunology, School of Basic Medical Sciences, Hubei University of Medicine, 30 Renmin Road, Shiyan, 442000, Hubei, People's Republic of China.
Hubei Key Laboratory of Embryonic Stem Cell Research, Hubei University of Medicine, Shiyan, 442000, Hubei, People's Republic of China.
Inflammopharmacology. 2024 Feb;32(1):849-861. doi: 10.1007/s10787-023-01396-6. Epub 2024 Jan 16.
Ulcerative colitis (UC) is a relapsing inflammatory disease with a unique aetiology. The treatment of UC is challenging, and the current clinical therapeutics for colitis have limited efficacy. Thus, finding new and effective treatment options remains urgent. Baricitinib, an inhibitor of Janus kinase (JAK), has been clinically used to treat rheumatoid arthritis (RA). However, its potential effects on UC have not been fully elucidated. In this study, we aimed to explore the effects of baricitinib on UC and its underlying mechanism. Dextran sulphate sodium (DSS)-induced murine model of chronic colitis was used to investigate the intervention efficacy following oral administration of baricitinib. The levels of key cytokines, such as IL-6, IFN-γ and IL-17A, were determined. Moreover, western blotting for IκBα, p-IκBα, JAK2, p-JAK2, STAT3 and p-STAT3 protein expression was performed to investigate the associated signalling pathways. Our findings demonstrated that baricitinib can significantly relieve DSS-induced UC in mice. After baricitinib intervention, IL-6, IFN-γ and IL-17A levels were decreased both in vitro and in vivo. Moreover, the elevated expression levels of p-IκBα, p-JAK2, and p-STAT3 were significantly reduced after treatment. Collectively, these results suggest that baricitinib is a potential therapeutic agent for alleviation of DSS-induced colitis. This study provides a method for subsequent investigations on potential curative drugs development of the for colitis.
溃疡性结肠炎(UC)是一种具有独特病因的复发性炎症性疾病。UC 的治疗具有挑战性,目前用于结肠炎的临床治疗方法疗效有限。因此,寻找新的有效治疗方法仍然迫在眉睫。巴利昔替尼是一种 Janus 激酶(JAK)抑制剂,已在临床上用于治疗类风湿关节炎(RA)。然而,其在 UC 中的潜在作用尚未得到充分阐明。在本研究中,我们旨在探讨巴利昔替尼对 UC 的影响及其潜在机制。我们使用葡聚糖硫酸钠(DSS)诱导的慢性结肠炎小鼠模型,研究了巴利昔替尼口服给药后的干预效果。测定了关键细胞因子(如 IL-6、IFN-γ 和 IL-17A)的水平。此外,还进行了 IκBα、p-IκBα、JAK2、p-JAK2、STAT3 和 p-STAT3 蛋白表达的 Western blot 分析,以研究相关信号通路。我们的研究结果表明,巴利昔替尼可以显著缓解 DSS 诱导的 UC 小鼠的疾病。巴利昔替尼干预后,体外和体内的 IL-6、IFN-γ 和 IL-17A 水平均降低。此外,治疗后 p-IκBα、p-JAK2 和 p-STAT3 的上调表达水平显著降低。综上所述,这些结果表明巴利昔替尼是缓解 DSS 诱导的结肠炎的潜在治疗药物。本研究为后续研究开发潜在的结肠炎治疗药物提供了一种方法。