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Publication
Soluble epoxide hydrolase pharmacological inhibition decreases alveolar bone
loss by modulating host inflammatory response, RANK-related signaling, ER stress
and apoptosis.
Authors Trindade da Silva CA, Bettaieb A, Napimoga MH, Lee KS, Inceoglu B, Ueira-Vieira
C, Bruun D, Goswami SK, Haj FG, Hammock BD
Submitted By Submitted Externally on 5/1/2017
Status Published
Journal The Journal of pharmacology and experimental therapeutics
Year 2017
Date Published 3/1/2017
Volume : Pages Not Specified : Not Specified
PubMed Reference 28356494
Abstract Epoxyeicosatrienoic acids (EETs), metabolites of arachidonic acid derived from
the cytochrome P450 (CYP450) enzymes, are mainly metabolized by soluble epoxide
hydrolase (sEH) to their corresponding diols. EETs but not their diols, have
anti-inflammatory properties and inhibition of sEH might provide protective
effects against inflammatory bone loss. Thus, in the present study, we tested
the selective sEH inhibitor,
1-trifluoromethoxyphenyl-3-(1-propionylpiperidin-4-yl) urea (TPPU) in a mouse
model of periodontitis induced by infection with A. actinomycetemcomitans. Oral
treatment of wild type mice with TPPU and sEH knockout (KO) animals showed
reduced bone loss induced by A. actinomycetemcomitans. This was associated with
decreased expression of key osteoclastogenic molecules RANK/RANKL/OPG and the
chemokine MCP-1 in the gingival tissue without affecting bacterial counts. In
addition, downstream kinases p38 and JNK known to be activated in response to
inflammatory signals were abrogated after TPPU treatment or in sEH KO mice.
Moreover, endoplasmic reticulum stress was elevated in periodontal disease but
was abrogated after TPPU treatment and in sEH knockout mice. Together, these
results demonstrated that sEH pharmacological inhibition may be of therapeutic
value in periodontitis.




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