Soluble epoxide hydrolase inhibitor promotes immunomodulation to inhibit bone resorption

M. H. Napimoga, E. P. Rocha, C. A. Trindade-da-Silva, A. P.D. Demasi, E. F. Martinez, C. G. Macedo, H. B. Abdalla, A. Bettaieb, F. G. Haj, J. T. Clemente-Napimoga, B. Inceoglu, Bruce D Hammock

Research output: Contribution to journalArticle

2 Scopus citations

Abstract

Background and Objective: Soluble epoxide hydrolase (sEH) is an enzyme in the arachidonate cascade which converts epoxy fatty acids (EpFAs), such as epoxyeicosatrienoic acids (EETs) produced by cytochrome P450 enzymes, to dihydroxy-eicosatrienoic acids. In the last 20 years with the development of inhibitors to sEH it has been possible to increase the levels of EETs and other EpFAs in in vivo models. Recently, studies have shown that EETs play a key role in blocking inflammation in a bone resorption process, but the mechanism is not clear. In the current study we used the sEH inhibitor (1-trifluoromethoxyphenyl-3-(1-propionylpiperidin-4-yl) urea [TPPU]) to investigate the immunomodulatory effects in a mouse periodontitis model. Material and Methods: Mice were infected on days 0, 2, and 4 with Aggregatibacter actinomycetemcomitans and divided into groups (n = 6) that were treated orally, daily for 15 days, with 1 mg/kg of TPPU. Then, the mice were killed and their jaws were analyzed for bone resorption using morphometry. Immunoinflammatory markers in the gingival tissue were analyzed by microarray PCR or western blotting. Results: Infected mice treated with TPPU showed lower bone resorption than infected mice without treatment. Interestingly, infected mice showed increased expression of sEH; however, mice treated with TPPU had a reduction in expression of sEH. Besides, several proinflammatory cytokines and molecular markers were downregulated in the gingival tissue in the group treated with 1 mg/kg of TPPU. Conclusion: The sEH inhibitor, TPPU, showed immunomodulatory effects, decreasing bone resorption and inflammatory responses in a bone resorption mouse model.

Original languageEnglish (US)
Pages (from-to)743-749
Number of pages7
JournalJournal of Periodontal Research
Volume53
Issue number5
DOIs
StatePublished - Oct 1 2018

Keywords

  • bone
  • epoxyeicosatrienoic acid
  • inflammation
  • periodontitis
  • soluble epoxide hydrolase
  • TPPU

ASJC Scopus subject areas

  • Periodontics

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  • Cite this

    Napimoga, M. H., Rocha, E. P., Trindade-da-Silva, C. A., Demasi, A. P. D., Martinez, E. F., Macedo, C. G., Abdalla, H. B., Bettaieb, A., Haj, F. G., Clemente-Napimoga, J. T., Inceoglu, B., & Hammock, B. D. (2018). Soluble epoxide hydrolase inhibitor promotes immunomodulation to inhibit bone resorption. Journal of Periodontal Research, 53(5), 743-749. https://doi.org/10.1111/jre.12559