4-Methylumbelliferone treatment and hyaluronan inhibition as a therapeutic strategy in inflammation, autoimmunity, and cancer

Hyaluronan (HA) is a prominent component of the extracellular matrix (ECM) at many sites of chronic inflammation, including type 1 diabetes (T1D), multiple sclerosis (MS), and numerous malignancies. Recent publications have demonstrated that when HA synthesis is inhibited using 4-methylumbelliferone...

Πλήρης περιγραφή

Λεπτομέρειες βιβλιογραφικής εγγραφής
Κύριοι συγγραφείς: Nadine eNagy, Hedwich F. Kuipers, Adam R. Frymoyer, Heather D. Ishak, Jennifer B. Bollyky, Thomas N. Wight, Paul L. Bollyky
Μορφή: Άρθρο
Γλώσσα:English
Έκδοση: Frontiers Media S.A. 2015-03-01
Σειρά:Frontiers in Immunology
Θέματα:
Διαθέσιμο Online:http://journal.frontiersin.org/Journal/10.3389/fimmu.2015.00123/full
Περιγραφή
Περίληψη:Hyaluronan (HA) is a prominent component of the extracellular matrix (ECM) at many sites of chronic inflammation, including type 1 diabetes (T1D), multiple sclerosis (MS), 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.
ISSN:1664-3224