title: Treatment with the hyaluronic acid synthesis inhibitor 4-methylumbelliferone suppresses SEB-induced lung inflammation.
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.
authors.affiliation: Division of Basic Medical Sciences, Mercer University School of Medicine, 1550 College St, Macon, GA 31207, USA. mckallip_r@mercer.edu.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: McKallip
authors.forename: Harriet F
authors.initials: HF
authors.lastname: Hagele
authors.forename: Olga N
authors.initials: ON
authors.lastname: Uchakina
mesh_terms: D055371:Acute Lung Injury / Q000188:drug therapy / Q000276:immunology; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D002199:Capillary Permeability / Q000187:drug effects; D049109:Cell Proliferation; D016207:Cytokines / Q000276:immunology; D004768:Enterotoxins; D014453:Glucuronosyltransferase / Q000037:antagonists & inhibitors*; D000076002:Hyaluronan Synthases; D006820:Hyaluronic Acid / Q000276:immunology*; D006923:Hymecromone / Q000627:therapeutic use*; D007962:Leukocytes / Q000166:cytology / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D011014:Pneumonia / Q000188:drug therapy* / Q000276:immunology; D013601:T-Lymphocytes / Q000187:drug effects
chemical_list: D000893:Anti-Inflammatory Agents; D016207:Cytokines; D004768:Enterotoxins; C031818:enterotoxin B, staphylococcal; D006923:Hymecromone; D006820:Hyaluronic Acid; D014453:Glucuronosyltransferase; D000076002:Hyaluronan Synthases