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Toxins 2013, 5(10), 1814-1826; doi:10.3390/toxins5101814

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

* ,
Division of Basic Medical Sciences, Mercer University School of Medicine, 1550 College St, Macon, GA 31207, USA
* Author to whom correspondence should be addressed.
Received: 14 August 2013 / Revised: 3 October 2013 / Accepted: 12 October 2013 / Published: 17 October 2013
(This article belongs to the Special Issue Enterotoxins: Microbial Proteins and Host Cell Dysregulation)
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Exposure to bacterial superantigens, such as staphylococcal enterotoxin B (SEB), can lead to the induction of acute lung injury/acute respiratory distress syndrome (ALI/ARDS). To date, there are no known effective treatments for SEB-induced inflammation. In the current study we investigated the potential use of the hyaluronic acid synthase inhibitor 4-methylumbelliferone (4-MU) on staphylococcal enterotoxin B (SEB) induced acute lung inflammation. Culturing SEB-activated immune cells with 4-MU led to reduced proliferation, reduced cytokine production as well as an increase in apoptosis when compared to untreated cells. Treatment of mice with 4-MU led to protection from SEB-induced lung injury. Specifically, 4-MU treatment led to a reduction in SEB-induced HA levels, reduction in lung permeability, and reduced pro-inflammatory cytokine production. Taken together, these results suggest that use of 4-MU to target hyaluronic acid production may be an effective treatment for the inflammatory response following exposure to SEB.
Keywords: staphylococcal enterotoxin B; acute lung injury; hyaluronic acid staphylococcal enterotoxin B; acute lung injury; hyaluronic acid
This is an open access article distributed under the Creative Commons Attribution License (CC BY) which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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McKallip, R.J.; Hagele, H.F.; Uchakina, O.N. Treatment with the Hyaluronic Acid Synthesis Inhibitor 4-Methylumbelliferone Suppresses SEB-Induced Lung Inflammation. Toxins 2013, 5, 1814-1826.

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