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 language | English (US) |
|---|---|
| Pages (from-to) | 9772-9777 |
| Number of pages | 6 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Volume | 102 |
| Issue number | 28 |
| DOIs | |
| State | Published - Jul 12 2005 |
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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 journal › Article
}
TY - JOUR
T1 - Soluble epoxide hydrolase is a therapeutic target for acute inflammation
AU - Schmelzer, Kara R.
AU - Kubala, Lukas
AU - Newman, John W.
AU - Kim, In Hae
AU - Eiserich, Jason P.
AU - Hammock, Bruce D.
PY - 2005/7/12
Y1 - 2005/7/12
N2 - 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.
AB - 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.
KW - Cydooxygenase
KW - Epoxygenase
KW - Lipoxin A
KW - Lipoxygenase
KW - Proinflammatory mediators
UR - http://www.scopus.com/inward/record.url?scp=22244443733&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=22244443733&partnerID=8YFLogxK
U2 - 10.1073/pnas.0503279102
DO - 10.1073/pnas.0503279102
M3 - Article
VL - 102
SP - 9772
EP - 9777
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
SN - 0027-8424
IS - 28
ER -