Soluble epoxide hydrolase is a therapeutic target for acute inflammation

Kara R. Schmelzer, Lukas Kubala, John W. Newman, In Hae Kim, Jason P. Eiserich, Bruce D. Hammock

Research output: Contribution to journalArticle

298 Citations (Scopus)

Abstract

As of 2004, >73 million people were prescribed antiinflammatory 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.

Original languageEnglish (US)
Pages (from-to)9772-9777
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume102
Issue number28
DOIs
StatePublished - Jul 12 2005

Fingerprint

Epoxide Hydrolases
Inflammation
Lipoxins
Acute Disease
Therapeutics
Inbred C57BL Mouse
Hypotension
Lipopolysaccharides
Urea
Nitric Oxide
Anti-Inflammatory Agents
Pharmacology
Cytokines
Mortality
Wounds and Injuries

Keywords

  • Cydooxygenase
  • Epoxygenase
  • Lipoxin A
  • Lipoxygenase
  • Proinflammatory mediators

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

Soluble epoxide hydrolase is a therapeutic target for acute inflammation. / Schmelzer, Kara R.; Kubala, Lukas; Newman, John W.; Kim, In Hae; Eiserich, Jason P.; Hammock, Bruce D.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 102, No. 28, 12.07.2005, p. 9772-9777.

Research output: Contribution to journalArticle

Schmelzer, Kara R. ; Kubala, Lukas ; Newman, John W. ; Kim, In Hae ; Eiserich, Jason P. ; Hammock, Bruce D. / Soluble epoxide hydrolase is a therapeutic target for acute inflammation. In: Proceedings of the National Academy of Sciences of the United States of America. 2005 ; Vol. 102, No. 28. pp. 9772-9777.
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