Treatment with the hyaluronic Acid synthesis inhibitor 4-methylumbelliferone suppresses LPS-induced lung inflammation.

Abstract

Exposure to bacterial endotoxins, such as lipopolysaccharide (LPS), can lead to the induction of acute lung injury/acute respiratory distress syndrome (ALI/ARDS). To date, there are no known effective treatments for LPS-induced inflammation. In the current study, we investigated the potential use of the hyaluronic acid (HA) synthesis inhibitor 4-methylumbelliferone (4-MU) on LPS-induced acute lung inflammation. Culturing LPS-activated immune cells with 4-MU led to reduced proliferation, reduced cytokine production, and an increase in apoptosis when compared to untreated cells. Treatment of mice with 4-MU led to protection from LPS-induced lung injury. Specifically, 4-MU treatment led to a reduction in LPS-induced hyaluronic acid synthase (HAS) messenger RNA (mRNA) levels, reduction in lung permeability, and reduction in proinflammatory cytokine production. Taken together, these results suggest that use of 4-MU to target HA production may be an effective treatment for the inflammatory response following exposure to LPS.

• Authors: Robert J McKallip, Hao Ban, Olga N Uchakina
• Journal: Inflammation (Inflammation) Vol. 38 Issue 3 Pg. 1250-9 ( 2015) ISSN: 1573-2576 [Electronic] United States
• PMID: 25537799 (Publication Type: Journal Article)

Chemical References

• Cytokines
• Lipopolysaccharides
• RNA, Messenger
• Hymecromone
• Hyaluronic Acid
• Glucuronosyltransferase
• Hyaluronan Synthases

Topics

• Acute Lung Injury (drug therapy)
• Animals
• Apoptosis (drug effects)
• Cell Proliferation (drug effects)
• Cells, Cultured
• Cytokines (biosynthesis)
• Disease Models, Animal
• Glucuronosyltransferase (antagonists & inhibitors, biosynthesis, genetics)
• Hyaluronan Synthases
• Hyaluronic Acid (biosynthesis)
• Hymecromone (therapeutic use)
• Inflammation (drug therapy, pathology)
• Lipopolysaccharides
• Lung (pathology)
• Mice
• Mice, Inbred C57BL
• Pneumonia (chemically induced, drug therapy, pathology)
• RNA, Messenger (genetics)
• Respiratory Distress Syndrome (drug therapy)
• Spleen (cytology)