15d-PGJ2 -loaded nanocapsules ameliorate experimental gout arthritis by reducing pain and inflammation in a PPAR-gamma-sensitive manner in mice

Scientific Reports
Kenji W Ruiz-MiyazawaWaldiceu A Verri

Abstract

Gout arthritis (GA) is a painful inflammatory disease in response to monosodium urate (MSU) crystals in the joints. 15deoxy-Δ12,14-prostaglandin J2 (15d-PGJ2) is a natural activator of PPAR-γ with analgesic, anti-inflammatory, and pro-resolution properties. Thus, we aimed to evaluate the effect and mechanisms of action of 15d-PGJ2 nanocapsules (NC) in the model of GA in mice, since a reduction of 33-fold in the dose of 15d-PGJ2 has been reported. Mice were treated with 15d-PGJ2-loaded NC, inert NC, free 15d-PGJ2 (without NC), or 15d-PGJ2-loaded NC+ GW9662, a PPAR-γ inhibitor. We show that 15d-PGJ2-loaded NC provided analgesic effect in a dose that the free 15d-PGJ2 failed to inhibiting pain and inflammation. Hence, 15d-PGJ2-loaded NC reduced MSU-induced IL-1β, TNF-α, IL-6, IL-17, and IL-33 release and oxidative stress. Also, 15d-PGJ2-loaded NC decreased the maturation of IL-1β in LPS-primed BMDM triggered by MSU. Further, 15d-PGJ2-loaded NC decreased the expression of the components of the inflammasome Nlrp3, Asc, and Pro-caspase-1, as consequence of inhibiting NF-κB activation. All effects were PPAR-γ-sensitive. Therefore, we demonstrated that 15d-PGJ2-loaded NC present analgesic and anti-inflammatory properties in a PPAR-γ-de...Continue Reading

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Citations

May 14, 2020·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Carlos A Trindade-da-SilvaMarcelo H Napimoga
Feb 28, 2019·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Yoshiki TsubosakaTakahisa Murata
Jan 23, 2019·Frontiers in Pharmacology·Izabela GalvãoMauro Martins Teixeira
Aug 2, 2019·Clinical Rheumatology·Juan WangHejian Zou
Oct 8, 2020·Scandinavian Journal of Immunology·Qi ChengYan Du
Jan 21, 2021·Neuroreport·Diogo F S SantosMaria C G Oliveira-Fusaro
Nov 2, 2020·Joint, Bone, Spine : Revue Du Rhumatisme·Viola KlückLeo A B Joosten
May 18, 2021·Frontiers in Pharmacology·Ruizhen HuangHonglin Hu

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Methods Mentioned

BETA
confocal microscopy
ABTS
ELISA
nanoprecipitation
Transmission electron microscopy

Software Mentioned

GraphPad
Nanosurf
Prism

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