hymecromone and Pneumonia

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.

Topics: Acute Lung Injury; Animals; Apoptosis; Cell Proliferation; Cells, Cultured; Cytokines; Disease Models, Animal; Glucuronosyltransferase; Hyaluronan Synthases; Hyaluronic Acid; Hymecromone; Inflammation; Lipopolysaccharides; Lung; Mice; Mice, Inbred C57BL; Pneumonia; Respiratory Distress Syndrome; RNA, Messenger; Spleen

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.

Topics: Acute Lung Injury; Animals; Anti-Inflammatory Agents; Apoptosis; Capillary Permeability; Cell Proliferation; Cytokines; Enterotoxins; Glucuronosyltransferase; Hyaluronan Synthases; Hyaluronic Acid; Hymecromone; Leukocytes; Mice; Mice, Inbred C57BL; Pneumonia; T-Lymphocytes