Anti-inflammatory effects of LCB 03-0110 on human corneal epithelial and murine T helper 17 cells.

IF 1.6 4区 医学 Q3 PHARMACOLOGY & PHARMACY
Do Vinh Truong, Beom-Seok Yang, Chiman Song
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引用次数: 0

Abstract

Dry eye disease (DED) is a complicated disorder that impacts ocular surface and tear-film stability. Inflammation has recently been reported as the core mechanism and main therapeutic target of DED. Although anti-inflammatory drugs have been developed, they still have limited efficacy and various side effects. Recent reports have suggested that kinase inhibitors are beneficial for relieving inflammation. Therefore, this study aimed to investigate the anti-inflammatory effects of LCB 03-0110, a multi-tyrosine kinase inhibitor, on representative cell-based models (HCE- 2 and Th17 cells) of DED. While tacrolimus and tofacitinib, two different anti-inflammatory drugs that have entered clinical trials for DED treatment, did not induce any anti-inflammatory responses in HCE-2 cells, LCB 03-0110 significantly suppressed the phosphorylation of P38 and ERK and reduced the expression levels of IL-6 and IL-8 in HCE-2 cells treated with either LPS or poly(I:C). Moreover, LCB 03-0110 notably decreased the expression level of IL-17A in Th17 cells in a dose-dependent manner, whereas tofacitinib promoted IL-17A production at low concentrations but inhibited its expression at concentrations greater than 1 μM. In addition, LCB 03-0110 was found to be non-toxic to both HCE-2 and Th17 cells. In conclusion, these results suggest that LCB 03-0110 would be a promising drug candidate for the treatment of DED because of its advantages over tacrolimus and tofacitinib.

LCB 03-0110 对人类角膜上皮细胞和小鼠 T 辅助细胞 17 的抗炎作用。
干眼症(DED)是一种影响眼表和泪膜稳定性的复杂疾病。最近有报道称,炎症是 DED 的核心机制和主要治疗目标。虽然抗炎药物已经开发出来,但它们的疗效仍然有限,而且存在各种副作用。最近有报道称,激酶抑制剂有利于缓解炎症。因此,本研究旨在探讨多种酪氨酸激酶抑制剂 LCB 03-0110 对 DED 的代表性细胞模型(HCE- 2 和 Th17 细胞)的抗炎作用。虽然他克莫司和托法替尼这两种已进入临床试验的治疗 DED 的不同抗炎药物在 HCE-2 细胞中没有诱导任何抗炎反应,但 LCB 03-0110 能显著抑制 P38 和 ERK 的磷酸化,并降低经 LPS 或 poly(I:C) 处理的 HCE-2 细胞中 IL-6 和 IL-8 的表达水平。此外,LCB 03-0110 还能以剂量依赖的方式显著降低 Th17 细胞中 IL-17A 的表达水平,而托法替尼在低浓度时能促进 IL-17A 的产生,但在浓度大于 1 μM 时则会抑制其表达。此外,LCB 03-0110 对 HCE-2 和 Th17 细胞均无毒性。总之,这些结果表明,与他克莫司和托法替尼相比,LCB 03-0110具有优势,有望成为治疗DED的候选药物。
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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来源期刊
Korean Journal of Physiology & Pharmacology
Korean Journal of Physiology & Pharmacology PHARMACOLOGY & PHARMACY-PHYSIOLOGY
CiteScore
3.20
自引率
5.00%
发文量
53
审稿时长
6-12 weeks
期刊介绍: The Korean Journal of Physiology & Pharmacology (Korean J. Physiol. Pharmacol., KJPP) is the official journal of both the Korean Physiological Society (KPS) and the Korean Society of Pharmacology (KSP). The journal launched in 1997 and is published bi-monthly in English. KJPP publishes original, peer-reviewed, scientific research-based articles that report successful advances in physiology and pharmacology. KJPP welcomes the submission of all original research articles in the field of physiology and pharmacology, especially the new and innovative findings. The scope of researches includes the action mechanism, pharmacological effect, utilization, and interaction of chemicals with biological system as well as the development of new drug targets. Theoretical articles that use computational models for further understanding of the physiological or pharmacological processes are also welcomed. Investigative translational research articles on human disease with an emphasis on physiology or pharmacology are also invited. KJPP does not publish work on the actions of crude biological extracts of either unknown chemical composition (e.g. unpurified and unvalidated) or unknown concentration. Reviews are normally commissioned, but consideration will be given to unsolicited contributions. All papers accepted for publication in KJPP will appear simultaneously in the printed Journal and online.
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