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Treatment with the Hyaluronic Acid Synthesis Inhibitor 4-Methylumbelliferone Suppresses LPS-Induced Lung Inflammation

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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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Authors and Affiliations

  1. Division of Basic Medical Sciences, Mercer University School of Medicine, 1550 College St, Macon, GA, 31207, USA

    Robert J. McKallip, Hao Ban & Olga N. Uchakina

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  1. Robert J. McKallip
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  2. Hao Ban
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Correspondence to Robert J. McKallip.

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McKallip, R.J., Ban, H. & Uchakina, O.N. Treatment with the Hyaluronic Acid Synthesis Inhibitor 4-Methylumbelliferone Suppresses LPS-Induced Lung Inflammation. Inflammation 38, 1250–1259 (2015). https://doi.org/10.1007/s10753-014-0092-y

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