Nagy Nadine, Kuipers Hedwich F, Frymoyer Adam R, Ishak Heather D, Bollyky Jennifer B, Wight Thomas N, Bollyky Paul L
Division of Infectious Diseases and Geographic Medicine, Department of Medicine, Stanford University School of Medicine , Stanford, CA , USA.
Department of Pediatrics, Stanford University School of Medicine , Stanford, CA , USA.
Front Immunol. 2015 Mar 23;6:123. doi: 10.3389/fimmu.2015.00123. eCollection 2015.
Hyaluronan (HA) is a prominent component of the extracellular matrix at many sites of chronic inflammation, including type 1 diabetes (T1D), multiple sclerosis, and numerous malignancies. Recent publications have demonstrated that when HA synthesis is inhibited using 4-methylumbelliferone (4-MU), beneficial effects are observed in several animal models of these diseases. Notably, 4-MU is an already approved drug in Europe and Asia called "hymecromone" where it is used to treat biliary spasm. However, there is uncertainty regarding how 4-MU treatment provides benefit in these animal models and the potential long-term consequences of HA inhibition. Here, we review what is known about how HA contributes to immune dysregulation and tumor progression. Then, we review what is known about 4-MU and hymecromone in terms of mechanism of action, pharmacokinetics, and safety. Finally, we review recent studies detailing the use of 4-MU to treat animal models of cancer and autoimmunity.
透明质酸（HA）是慢性炎症许多部位细胞外基质的重要组成部分，包括1型糖尿病（T1D）、多发性硬化症和多种恶性肿瘤。最近的出版物表明，当使用4-甲基伞形酮（4-MU）抑制HA合成时，在这些疾病的几种动物模型中观察到了有益效果。值得注意的是，4-MU在欧洲和亚洲是一种已获批的药物，名为“hymecromone”，用于治疗胆道痉挛。然而，关于4-MU治疗如何在这些动物模型中产生益处以及HA抑制的潜在长期后果尚不确定。在此，我们综述了关于HA如何导致免疫失调和肿瘤进展的已知信息。然后，我们从作用机制、药代动力学和安全性方面综述了关于4-MU和hymecromone的已知信息。最后，我们综述了最近详细介绍使用4-MU治疗癌症和自身免疫动物模型的研究。
