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

RJ McKallip, H Ban, ON Uchakina - Inflammation, 2015 - Springer
RJ McKallip, H Ban, ON Uchakina
Inflammation, 2015Springer
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 …
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.
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