Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 102, Issue 28, Pages 9772-9777Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0503279102
Keywords
cyclooxygenase; lipoxin A(4); lipoxygenase; proinflammatory mediators; epoxygenase
Categories
Funding
- NIEHS NIH HHS [P01 ES011269, T32 ES 007505 9, P42 ES 04699, 1P01 ES 11269, P30 ES005707, P42 ES004699, P30 ES 05707, R37 ES 02710, R37 ES002710] Funding Source: Medline
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As of 2004, > 73 million people were prescribed anti inflammatory medication. Despite the extensive number of current products, many people still suffer from their diseases or the pharmacological properties (side effects) of the medications. Therefore, developing therapeutic strategies to treat inflammation remains an important endeavor. Here, we demonstrate that the soluble epoxide hydrolase (sEH) is a key pharmacologic target for treating acute systemic inflammation. Lipopolysaccharide-induced mortality, systemic hypotension, and histologically evaluated tissue injury were substantially diminished by administration of urea-based, small-molecule inhibitors of sEH to C57BL/6 mice. Moreover, sEH inhibitors decreased plasma levels of proinflammatory cytokines and nitric oxide metabolites while promoting the formation of lipoxins, thus supporting inflammatory resolution. These data suggest that sEH inhibitors have therapeutic efficacy in the treatment and management of acute inflammatory diseases.
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