PMID- 38117781
OWN - NLM
STAT- MEDLINE
DCOM- 20240118
LR  - 20240415
IS  - 1550-6606 (Electronic)
IS  - 0022-1767 (Print)
IS  - 0022-1767 (Linking)
VI  - 212
IP  - 3
DP  - 2024 Feb 1
TI  - Modulating the sEH/EETs Axis Restrains Specialized Proresolving Mediator 
      Impairment and Regulates T Cell Imbalance in Experimental Periodontitis.
PG  - 433-445
LID - 10.4049/jimmunol.2300650 [doi]
AB  - 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.
CI  - Copyright (c) 2024 by The American Association of Immunologists, Inc.
FAU - Abdalla, Henrique B
AU  - Abdalla HB
AD  - Department of Applied Oral Sciences, The Forsyth Institute, Cambridge, MA.
AD  - Faculdade Sao Leopoldo Mandic, Campinas, Brazil.
FAU - Puhl, Luciano
AU  - Puhl L
AUID- ORCID: 0000-0003-0151-6861
AD  - Faculdade Sao Leopoldo Mandic, Campinas, Brazil.
FAU - Rivas, Carla Alvarez
AU  - Rivas CA
AD  - Department of Applied Oral Sciences, The Forsyth Institute, Cambridge, MA.
AD  - Harvard School of Dental Medicine, Boston, MA.
FAU - Wu, Yu-Chiao
AU  - Wu YC
AD  - Department of Applied Oral Sciences, The Forsyth Institute, Cambridge, MA.
AD  - Harvard School of Dental Medicine, Boston, MA.
FAU - Rojas, Paola
AU  - Rojas P
AD  - Department of Applied Oral Sciences, The Forsyth Institute, Cambridge, MA.
FAU - Trindade-da-Silva, Carlos Antonio
AU  - Trindade-da-Silva CA
AD  - Faculdade Sao Leopoldo Mandic, Campinas, Brazil.
FAU - Hammock, Bruce D
AU  - Hammock BD
AD  - Department of Entomology and UCD Comprehensive Cancer Center, University of 
      California, Davis, CA.
FAU - Maddipati, Krishna R
AU  - Maddipati KR
AUID- ORCID: 0000-0003-1445-791X
AD  - Department of Pathology, Wayne State University, Detroit, MI.
FAU - Soares, Mariana Q S
AU  - Soares MQS
AUID- ORCID: 0000-0002-9387-3729
AD  - Departamento de Radiologia, Faculdade Sao Leopoldo Mandic, Campinas, Brazil.
FAU - Clemente-Napimoga, Juliana T
AU  - Clemente-Napimoga JT
AUID- ORCID: 0000-0003-1068-3039
AD  - Faculdade Sao Leopoldo Mandic, Campinas, Brazil.
FAU - Kantarci, Alpdogan
AU  - Kantarci A
AD  - Department of Applied Oral Sciences, The Forsyth Institute, Cambridge, MA.
FAU - Napimoga, Marcelo H
AU  - Napimoga MH
AUID- ORCID: 0000-0003-4472-365X
AD  - Faculdade Sao Leopoldo Mandic, Campinas, Brazil.
FAU - Van Dyke, Thomas E
AU  - Van Dyke TE
AUID- ORCID: 0000-0003-0568-124X
AD  - Department of Applied Oral Sciences, The Forsyth Institute, Cambridge, MA.
AD  - Department of Oral Medicine, Infection, and Immunity, Faculty of Medicine, 
      Harvard University, Boston, MA.
LA  - eng
GR  - R35 ES030443/ES/NIEHS NIH HHS/United States
GR  - P42 ES004699/ES/NIEHS NIH HHS/United States
GR  - S10 OD032292/OD/NIH HHS/United States
GR  - R01 DE025020/DE/NIDCR NIH HHS/United States
GR  - S10 RR027926/RR/NCRR NIH HHS/United States
PT  - Journal Article
PL  - United States
TA  - J Immunol
JT  - Journal of immunology (Baltimore, Md. : 1950)
JID - 2985117R
RN  - 0 (Eicosanoids)
RN  - EC 3.3.2.- (Epoxide Hydrolases)
SB  - IM
MH  - Humans
MH  - Animals
MH  - Mice
MH  - X-Ray Microtomography
MH  - *Periodontitis/metabolism
MH  - Inflammation
MH  - Eicosanoids
MH  - *Bone Resorption
MH  - Epoxide Hydrolases/metabolism
PMC - PMC10866374
MID - NIHMS1960566
EDAT- 2023/12/20 18:42
MHDA- 2024/01/18 06:42
PMCR- 2025/02/01
CRDT- 2023/12/20 13:34
PHST- 2023/09/28 00:00 [received]
PHST- 2023/11/26 00:00 [accepted]
PHST- 2025/02/01 00:00 [pmc-release]
PHST- 2024/01/18 06:42 [medline]
PHST- 2023/12/20 18:42 [pubmed]
PHST- 2023/12/20 13:34 [entrez]
AID - 266559 [pii]
AID - 10.4049/jimmunol.2300650 [doi]
PST - ppublish
SO  - J Immunol. 2024 Feb 1;212(3):433-445. doi: 10.4049/jimmunol.2300650.