Departamento de Ciências Patológicas, Universidade Estadual de Londrina-UEL, Rod. Celso Garcia Cid, Km 380, PR445, 86057-970, Cx. Postal 10.011, Londrina, Paraná, Brazil.
Laboratory of Immunology and Molecular Biology, São Leopoldo Mandic Institute and Researcher Center, Campinas, Brazil.
Sci Rep. 2018 Sep 18;8(1):13979. doi: 10.1038/s41598-018-32334-0.
Gout arthritis (GA) is a painful inflammatory disease in response to monosodium urate (MSU) crystals in the joints. 15deoxy-Δ-prostaglandin J (15d-PGJ) 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-PGJ nanocapsules (NC) in the model of GA in mice, since a reduction of 33-fold in the dose of 15d-PGJ has been reported. Mice were treated with 15d-PGJ-loaded NC, inert NC, free 15d-PGJ (without NC), or 15d-PGJ-loaded NC+ GW9662, a PPAR-γ inhibitor. We show that 15d-PGJ-loaded NC provided analgesic effect in a dose that the free 15d-PGJ failed to inhibiting pain and inflammation. Hence, 15d-PGJ-loaded NC reduced MSU-induced IL-1β, TNF-α, IL-6, IL-17, and IL-33 release and oxidative stress. Also, 15d-PGJ-loaded NC decreased the maturation of IL-1β in LPS-primed BMDM triggered by MSU. Further, 15d-PGJ-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-PGJ-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-PGJ-loaded NC ameliorates MSU-induced GA in a PPAR-γ-sensitive manner.
痛风性关节炎（GA）是一种由关节中单钠尿酸盐（MSU）晶体引起的疼痛性炎症性疾病。15 脱氧-Δ-前列腺素 J（15d-PGJ）是一种天然的 PPAR-γ 激活剂，具有镇痛、抗炎和促解决的特性。因此，我们旨在评估 15d-PGJ 纳米囊（NC）在 GA 小鼠模型中的作用和作用机制，因为已经报道 15d-PGJ 的剂量减少了 33 倍。小鼠用负载 15d-PGJ 的 NC、惰性 NC、游离 15d-PGJ（无 NC）或负载 15d-PGJ 的 NC+GW9662（一种 PPAR-γ 抑制剂）治疗。我们表明，负载 15d-PGJ 的 NC 在自由 15d-PGJ 未能抑制疼痛和炎症的剂量下提供了镇痛作用。因此，负载 15d-PGJ 的 NC 减少了 MSU 诱导的 IL-1β、TNF-α、IL-6、IL-17 和 IL-33 的释放和氧化应激。此外，负载 15d-PGJ 的 NC 减少了 MSU 触发的 LPS 预刺激的 BMDM 中 IL-1β 的成熟。此外，负载 15d-PGJ 的 NC 降低了炎性小体 Nlrp3、Asc 和 Pro-caspase-1 的组成部分的表达，这是由于抑制 NF-κB 激活所致。所有作用均为 PPAR-γ 敏感。因此，我们证明负载 15d-PGJ 的 NC 以 PPAR-γ 依赖性方式呈现出镇痛和抗炎特性，抑制 GA 中 IL-1β 的释放和 NF-κB 的激活。总之，负载 15d-PGJ 的 NC 以 PPAR-γ 敏感的方式改善了 MSU 诱导的 GA。
