Modulating the sEH/EETs Axis Restrains Specialized Proresolving Mediator Impairment and Regulates T Cell Imbalance in Experimental Periodontitis.

Autor:	Abdalla HB; Department of Applied Oral Sciences, The Forsyth Institute, Cambridge, MA.; Faculdade São Leopoldo Mandic, Campinas, Brazil., Puhl L; Faculdade São Leopoldo Mandic, Campinas, Brazil., Rivas CA; Department of Applied Oral Sciences, The Forsyth Institute, Cambridge, MA.; Harvard School of Dental Medicine, Boston, MA., Wu YC; Department of Applied Oral Sciences, The Forsyth Institute, Cambridge, MA.; Harvard School of Dental Medicine, Boston, MA., Rojas P; Department of Applied Oral Sciences, The Forsyth Institute, Cambridge, MA., Trindade-da-Silva CA; Faculdade São Leopoldo Mandic, Campinas, Brazil., Hammock BD; Department of Entomology and UCD Comprehensive Cancer Center, University of California, Davis, CA., Maddipati KR; Department of Pathology, Wayne State University, Detroit, MI., Soares MQS; Departamento de Radiologia, Faculdade São Leopoldo Mandic, Campinas, Brazil., Clemente-Napimoga JT; Faculdade São Leopoldo Mandic, Campinas, Brazil., Kantarci A; Department of Applied Oral Sciences, The Forsyth Institute, Cambridge, MA., Napimoga MH; Faculdade São Leopoldo Mandic, Campinas, Brazil., Van Dyke TE; Department of Applied Oral Sciences, The Forsyth Institute, Cambridge, MA.; Department of Oral Medicine, Infection, and Immunity, Faculty of Medicine, Harvard University, Boston, MA.
Jazyk:	angličtina
Zdroj:	Journal of immunology (Baltimore, Md. : 1950) [J Immunol] 2024 Feb 01; Vol. 212 (3), pp. 433-445.
DOI:	10.4049/jimmunol.2300650
Abstrakt:	Epoxyeicosatrienoic acids (EETs) and other epoxy fatty acids are short-acting lipids involved in resolution of inflammation. Their short half-life, due to its metabolism by soluble epoxide hydrolase (sEH), limits their effects. Specialized proresolving mediators (SPMs) are endogenous regulatory lipids insufficiently synthesized in uncontrolled and chronic inflammation. Using an experimental periodontitis model, we pharmacologically inhibited sEH, examining its impact on T cell activation and systemic SPM production. In humans, we analyzed sEH in the gingival tissue of periodontitis patients. Mice were treated with sEH inhibitor (sEHi) and/or EETs before ligature placement and treated for 14 d. Bone parameters were assessed by microcomputed tomography and methylene blue staining. Blood plasma metabololipidomics were carried out to quantify SPM levels. We also determined T cell activation by reverse transcription-quantitative PCR and flow cytometry in cervical lymph nodes. Human gingival samples were collected to analyze sEH using ELISA and electrophoresis. Data reveal that pharmacological sEHi abrogated bone resorption and preserved bone architecture. Metabololipidomics revealed that sEHi enhances lipoxin A4, lipoxin B4, resolvin E2, and resolvin D6. An increased percentage of regulatory T cells over Th17 was noted in sEHi-treated mice. Lastly, inflamed human gingival tissues presented higher levels and expression of sEH than did healthy gingivae, being positively correlated with periodontitis severity. Our findings indicate that sEHi preserves bone architecture and stimulates SPM production, associated with regulatory actions on T cells favoring resolution of inflammation. Because sEH is enhanced in human gingivae from patients with periodontitis and connected with disease severity, inhibition may prove to be an attractive target for managing osteolytic inflammatory diseases. (Copyright © 2024 by The American Association of Immunologists, Inc.)
Databáze:	MEDLINE
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