TY - JOUR
T1 - 15d-PGJ2-loaded nanocapsules ameliorate experimental gout arthritis by reducing pain and inflammation in a PPAR-gamma-sensitive manner in mice
AU - Ruiz-Miyazawa, Kenji W.
AU - Staurengo-Ferrari, Larissa
AU - Pinho-Ribeiro, Felipe A.
AU - Fattori, Victor
AU - Zaninelli, Tiago H.
AU - Badaro-Garcia, Stephanie
AU - Borghi, Sergio M.
AU - Andrade, Ketlem C.
AU - Clemente-Napimoga, Juliana T.
AU - Alves-Filho, Jose C.
AU - Cunha, Thiago M.
AU - Fraceto, Leonardo F.
AU - Cunha, Fernando Q.
AU - Napimoga, Marcelo H.
AU - Casagrande, Rubia
AU - Verri, Waldiceu A.
N1 - Funding Information:
This work was supported by Pesquisa para o Sistema Único de Saúde (PPSUS) grant from Departamento de Ciência e Tecnologia da Secretaria de Ciência, Tecnologia e Insumos Estratégicos, Ministério da Saúde (Decit/SCTIE/MS, Brazil) intermediated by Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq, Brazil) with support of Fundação Araucária and Secretaria Estadual de Saúde, Paraná (SESA-PR, Brazil); São Paulo Research Foundation under grant agreements 2011/19670-0 (Thematic Project), 2010/15014-9 and 2013/08216-2 (Center for Research in Inflammatory Disease); Coordenadoria de Aperfeiçoamento de Pessoal de Nível Superior (CAPES, Brazil); and Financiadora de Estudos e Projetos and Secretaria de Estado da Ciência, Tecnologia e Ensino Superior do Paraná under grant agreements 01.12.0294.00 (0476/11) (FINEP/SETI-PR, Brazil). We thank the support of Central Multiusuário de Laboratórios de Pesquisa da Universidade Estadual de Londrina (CMLP-UEL).
Publisher Copyright:
© 2018, The Author(s).
PY - 2018/12/1
Y1 - 2018/12/1
N2 - 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-dependent manner inhibiting IL-1β release and NF-κB activation in GA. Concluding, 15d-PGJ2-loaded NC ameliorates MSU-induced GA in a PPAR-γ-sensitive manner.
AB - 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-dependent manner inhibiting IL-1β release and NF-κB activation in GA. Concluding, 15d-PGJ2-loaded NC ameliorates MSU-induced GA in a PPAR-γ-sensitive manner.
UR - http://www.scopus.com/inward/record.url?scp=85053504128&partnerID=8YFLogxK
U2 - 10.1038/s41598-018-32334-0
DO - 10.1038/s41598-018-32334-0
M3 - Article
C2 - 30228306
AN - SCOPUS:85053504128
SN - 2045-2322
VL - 8
JO - Scientific reports
JF - Scientific reports
IS - 1
M1 - 13979
ER -