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
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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)
Abstract
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. View Full-Text
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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.