Soluble Epoxide Hydrolase Inhibitor Promotes Immunomodulation to Inhibit Bone Resorption

Objectives: The soluble Epoxide Hydrolase (sEH) is an enzyme in the arachidonate cascade which converts epoxy fatty acids (EpFA) such as epoxyeicosatrienoic acids (EETs) produced by cytochrome P450 enzymes to dihydroxy-eicosatrienoic acids (DHETs). In last years with the development of inhibitors to sEH was possible to increase of EETs and other EpFA levels in vivo models. Recently, studies have shown that EETs play a key role in blocking inflammation in a bone resorption process, but this mechanism is not clear. In the current study we used the sEH inhibitor (TPPU) to investigate the immunomodulatory effects in a mouse periodontitis model.
Methods: Mice were infected on days 0, 2, and 4 with Aggregatibacter actinomycetemcomitans and divided into groups (n = 6) that were treated daily orally during 15 days with 1 mg/kg TPPU. The animals were sacrificed, and the jaws were analyzed for bone resorption by morphometry. Immunoinflammatory markers in the gingival tissue were analyzed by microarray PCR or Western blotting.
Results: Infected animals treated with TPPU showed lower bone resorption than infected animals without treatment. Interestingly, infected animals showed increased expression of sEH however; animals treated with TPPU had a reduction of the protein expression sEH. Besides, several proinflammatory cytokines and molecular markers were downregulated in the gingival tissue in the group treated with 1 mg/kg TPPU.
Conclusions: The sEH inhibitor (TPPU), showed immunomodulatory effects, decreasing bone resorption and inflammatory responses in a bone resorption mouse model.