Peroxisome proliferator-activated receptors alpha and beta mediate the anti-inflammatory effects of the cyclopentenone prostaglandin 15-deoxy-Δ 12,14 -PGJ 2 in fish granulocytes.

Autor: Gómez-Abellán V; Departamento de Biología Cellular e Histología, Facultad de Biología, Universidad de Murcia, 30100, Murcia, Spain; Instituto Murciano de Investigación Biosanitaria (IMIB)-Arrixaca, 30120, Murcia, Spain., Pérez-Oliva AB; Instituto Murciano de Investigación Biosanitaria (IMIB)-Arrixaca, 30120, Murcia, Spain; Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Instituto de Salud Carlos III, 28029, Madrid, Spain., Cabas I; Departamento de Biología Cellular e Histología, Facultad de Biología, Universidad de Murcia, 30100, Murcia, Spain; Instituto Murciano de Investigación Biosanitaria (IMIB)-Arrixaca, 30120, Murcia, Spain; Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Instituto de Salud Carlos III, 28029, Madrid, Spain., Hermi F; Unit of Immunology, Environmental Microbiology and Cancerously, Faculty of Sciences of Bizerte, Jarzouna, Bizerte, 7021, University of Carthage, Tunis, Tunisia., Arizcun M; Oceanographic Center of Murcia, Spanish Institute of Oceanography (IEO-CSIC), 30860, Murcia, Spain., García-Moreno D; Instituto Murciano de Investigación Biosanitaria (IMIB)-Arrixaca, 30120, Murcia, Spain; Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Instituto de Salud Carlos III, 28029, Madrid, Spain., Sepulcre MP; Departamento de Biología Cellular e Histología, Facultad de Biología, Universidad de Murcia, 30100, Murcia, Spain; Instituto Murciano de Investigación Biosanitaria (IMIB)-Arrixaca, 30120, Murcia, Spain; Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Instituto de Salud Carlos III, 28029, Madrid, Spain. Electronic address: mpsepul@um.es., Mulero V; Departamento de Biología Cellular e Histología, Facultad de Biología, Universidad de Murcia, 30100, Murcia, Spain; Instituto Murciano de Investigación Biosanitaria (IMIB)-Arrixaca, 30120, Murcia, Spain; Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Instituto de Salud Carlos III, 28029, Madrid, Spain. Electronic address: vmulero@um.es.
Jazyk: angličtina
Zdroj: Developmental and comparative immunology [Dev Comp Immunol] 2022 Nov; Vol. 136, pp. 104498. Date of Electronic Publication: 2022 Aug 07.
DOI: 10.1016/j.dci.2022.104498
Abstrakt: Prostaglandins (PGs) are highly reactive small lipophilic molecules derived from polyunsaturated fatty acids of the cell membrane and play a key role in the resolution of inflammation processes. 15-deoxy-Δ 12,14 -PGJ 2 (15dPGJ 2 ) is a cyclopentenone PG (CyPG) of the J series with anti-inflammatory, anti-proliferative and pro-apoptotic effects. This CyPG can signal through: (i) the PGD 2 receptor (DP2) and peroxisome proliferator-activated receptor γ (PPARγ) or (ii) by covalent binding to protein nucleophiles, such as, thiols groups of cysteine, lysine or histidine via a Michael addition reaction, modifying its structure and function. In this work we show that acidophilic granulocytes (AGs) of gilthead seabream (Sparus aurata L.), the functional equivalent to mammalian neutrophils, constitutively expressed ppara, pparb and pparg genes, the latter showing the highest expression and up-regulation when stimulated by bacterial DNA. In addition, we tested the ability of 15dPGJ 2, and its biotinylated analog, as well as several PPARγ ligands, to modulate reactive oxygen species (ROS) and/or cytokines production during a Toll like receptor (TLR)-mediated granulocyte response. Thus, 15dPGJ 2 was able to significantly decrease bacterial DNA-induced ROS production and transcript levels of pparg, interleukin-1β (il1b) and prostaglandin-endoperoxide synthase 2 (ptgs2). In contrast, its biotinylated analog was less potent and a higher dose was required to elicit the same effects on ROS production and cytokine expression. In addition, different PPARγ agonists were able to mimic the effects of 15dPGJ 2 . Conversely, the PPARγ antagonist T007097 abolished the effect of 15dPGJ 2 on DNA bacterial-induced ROS production. Surprisingly, transactivation assays revealed that both 15dPGJ 2 and its biotinylated analog signaled via Pparα and Pparβ, but not by Pparγ. These results were further confirmed by HPLC/MS analysis, where Pparβ was identified as an interactor of biotin-15dPGJ 2 in naïve and DNA-stimulated leukocytes. Taken together, our data show that 15dPGJ 2 acts both through Ppar activation and covalent binding to proteins in fish granulocytes and identify for the first time in vertebrates a role for Pparα and Pparβ in the resolution of inflammation mediated by 15dPGJ 2 .
(Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)
Databáze: MEDLINE
Externí odkaz: