Soluble epoxide hydrolase inhibitor promotes immunomodulation to inhibit bone resorption

Napimoga, Marcelo Henrique; Rocha, Ennio Paulo Calearo da Costa; Trindade‐da‐Silva, Carlos Antônio; Demasi, Ana Paula Dias; Martinez, Elizabeth Ferreira; Macedo, Cristina Gomes de; Abdalla, Henrique Ballassini; Bettaieb, Ahmed; Haj, Fawaz G.; Clemente-Napimoga, Juliana Trindade; Inceoglu, Bora; Hammock, Bruce D.

doi:10.1111/jre.12559

Cited by 19 publications

(12 citation statements)

References 52 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The effects of EPHX2 inhibition on inflammation are multiple. It decreases bone loss by modulating host inflammatory response in an inflammatory bone resorption experimental model, similar to what occurs in arthritis [77]. EPHX2 inhibition also ameliorates hyperalgesia, edema, and decreases the expression of important pro-inflammatory cytokines of Th1 and Th17 profiles, while increasing Treg cells in an experimental model of arthritis [78].…”

Section: Ephx2 Inhibitorsmentioning

confidence: 76%

The Multifaceted Role of Epoxide Hydrolases in Human Health and Disease

Gautheron

Jéru

2020

IJMS

View full text Add to dashboard Cite

Epoxide hydrolases (EHs) are key enzymes involved in the detoxification of xenobiotics and biotransformation of endogenous epoxides. They catalyze the hydrolysis of highly reactive epoxides to less reactive diols. EHs thereby orchestrate crucial signaling pathways for cell homeostasis. The EH family comprises 5 proteins and 2 candidate members, for which the corresponding genes are not yet identified. Although the first EHs were identified more than 30 years ago, the full spectrum of their substrates and associated biological functions remain partly unknown. The two best-known EHs are EPHX1 and EPHX2. Their wide expression pattern and multiple functions led to the development of specific inhibitors. This review summarizes the most important points regarding the current knowledge on this protein family and highlights the particularities of each EH. These different enzymes can be distinguished by their expression pattern, spectrum of associated substrates, sub-cellular localization, and enzymatic characteristics. We also reevaluated the pathogenicity of previously reported variants in genes that encode EHs and are involved in multiple disorders, in light of large datasets that were made available due to the broad development of next generation sequencing. Although association studies underline the pleiotropic and crucial role of EHs, no data on high-effect variants are confirmed to date.

show abstract

Section: Ephx2 Inhibitorsmentioning

confidence: 76%

The Multifaceted Role of Epoxide Hydrolases in Human Health and Disease

Gautheron

Jéru

2020

IJMS

View full text Add to dashboard Cite

show abstract

“…To assess bone resorption induced by ETO, the distance between the cementum‐enamel junction and the alveolar bone crest was measured 28 days after crown cementation 22,25 . The sham group demonstrated the lowest mean distance in the experimental period (Fig 1B).…”

Section: Resultsmentioning

confidence: 99%

“…Bone loss was quantified as previously described (n = 6 from each group) 22 . The mandibles were separated from the skull and immersed in 3% hydrogen peroxide overnight.…”

Section: Methodsmentioning

confidence: 99%

Occlusion Heightened by Metal Crown Cementation is Aggressive for Periodontal Tissues

Abdalla

Clemente‐Napimoga

Trindade‐da‐Silva

et al. 2020

Journal of Prosthodontics

Self Cite

View full text Add to dashboard Cite

Purpose To investigate the effect of experimental traumatic occlusion (ETO) induced by metal crowns on alveolar bone loss. Materials and Methods Metal crowns were custom‐made for the lower first molars with occlusal discrepancy of 0.4 and 0.7 mm from the maximum intercuspation. Thirty‐six animals were randomly divided into three groups (n = 12 animals per group): 0.4‐mm hyperocclusion group, 0.7‐mm hyperocclusion group and the sham group (no metal crown). Twenty‐eight days after crown cementation, the animals were euthanized and gingival tissue was collected to assess cytokine levels of IL‐17, IL‐6, and TNF‐α using enzyme‐linked immunosorbent assay (ELISA). Mandibles were stained with 1% methylene blue and alveolar bone levels were quantified. Western blotting was used to quantify the expression of receptor activator of nuclear factor κ B (RANK), and its ligand (RANKL), secreted osteoclastogenic factor of activated T cells (SOFAT) and TNF‐α‐converting enzyme (TACE). Also, mandibles were histologically processed and stained with hematoxylin and eosin, from which the presence of osteoclast‐like cells, multinucleated cells containing ≥3 nuclei was counted at 100× magnification. The data were analyzed using one‐way ANOVA and Tukey tests. Results Experimental occlusal trauma for 28 consecutive days significantly increased alveolar bone loss and multinucleated cell counts (p < 0.05). RANK, RANKL, SOFAT, TACE, IL‐6, and TNF‐α were significantly higher in gingival tissues of ETO groups (p < 0.05). IL‐17 titers were unchanged among the groups (p > 0.05). Conclusion Experimental traumatic occlusion activates and sustains bone resorption pathways in the periodontium inducing alveolar bone resorption. As the intensity of occlusal trauma increased, alternative osteoclastic pathways were activated, such as TACE and SOFAT.

show abstract

“…There is a growing body of evidence demonstrating both genetic and pharmacological inhibition of sEH abrogate the uncontrolled sterile inflammation in different settings [ 187 , 227 , 228 ]. For instance, Yang et al showed the sEH inhibitor, trans -4-{4-[3-(4-trifluoromethoxyphenyl)-ureido]-cyclohexyloxy}-benzoic acid (t-TUCB), increased concentrations of the anti-inflammatory EETs and simultaneously decreased the concentrations of type 2 T helper cells (Th2), cytokines (IL-4, IL-5) and chemokines as well as total cell and eosinophil numbers in the lung lavage of a murine ovalbumin (OVA) model of asthma [ 229 ].…”

Section: Anti-inflammatory Effects Of N-3 and N-6 Pufa-derived Epomentioning

confidence: 99%

Mitochondrial Dysfunction and Inflammaging in Heart Failure: Novel Roles of CYP-Derived Epoxylipids

Keshavarz-Bahaghighat

Darwesh

Sosnowski

et al. 2020

Cells

View full text Add to dashboard Cite

Age-associated changes leading to a decline in cardiac structure and function contribute to the increased susceptibility and incidence of cardiovascular diseases (CVD) in elderly individuals. Indeed, age is considered a risk factor for heart failure and serves as an important predictor for poor prognosis in elderly individuals. Effects stemming from chronic, low-grade inflammation, inflammaging, are considered important determinants in cardiac health; however, our understanding of the mechanisms involved remains unresolved. A steady decline in mitochondrial function is recognized as an important biological consequence found in the aging heart which contributes to the development of heart failure. Dysfunctional mitochondria contribute to increased cellular stress and an innate immune response by activating the NLRP-3 inflammasomes, which have a role in inflammaging and age-related CVD pathogenesis. Emerging evidence suggests a protective role for CYP450 epoxygenase metabolites of N-3 and N-6 polyunsaturated fatty acids (PUFA), epoxylipids, which modulate various aspects of the immune system and protect mitochondria. In this article, we provide insight into the potential roles N-3 and N-6 PUFA have modulating mitochondria, inflammaging and heart failure.

show abstract

Soluble epoxide hydrolase inhibitor promotes immunomodulation to inhibit bone resorption

Abstract: The sEH inhibitor, TPPU, showed immunomodulatory effects, decreasing bone resorption and inflammatory responses in a bone resorption mouse model.

Cited by 19 publications

References 52 publications

The Multifaceted Role of Epoxide Hydrolases in Human Health and Disease

The Multifaceted Role of Epoxide Hydrolases in Human Health and Disease

Occlusion Heightened by Metal Crown Cementation is Aggressive for Periodontal Tissues

Mitochondrial Dysfunction and Inflammaging in Heart Failure: Novel Roles of CYP-Derived Epoxylipids

Contact Info

Product

Resources

About