RAW 264.7 대식세포에서 마늘 유래 황 함유 화합물에 의한 요산 유도 inflammasome 활성화의 억제는 ROS 생성 차단과 연관성이 있음|RISS 상세보기

다국어 초록 (Multilingual Abstract)

Gout, a chronic inflammatory arthritic disease, is characterized by hyperuricemia. Gout can be induced by an inflammatory response to monosodium urate (MSU) crystals mediated by pro-inflammatory cytokine release following activation of the NOD-like receptor protein 3 (NLRP3) inflammasome. Many sulfur-containing phytochemical compounds in garlic (Allium sativum L.) are considered active ingredients because of their potential pharmacological benefits for various diseases, but their efficacy in NLRP3 inflammasome activation-mediated gout has not been demonstrated. In this study, we investigated whether diallyl disulfide (DADS) and diallyl trisulfide (DATS), representative garlic-derived sulfur compounds, have an inhibitory effect on MSU-induced NLRP3 inflammasome activation. Our results showed that under non-cytotoxic conditions, DADS and DATS significantly blocked nitric oxide production and interleukin (IL)-1β release in response to MSU in lipopolysaccharide (LPS)- primed RAW 264.7 macrophages. DADS and DATS also attenuated enhanced expression of NLRP3 and its adapter protein, apoptosis-associated speck-like protein, which was associated with downregulation of and caspase-1 p20 and IL-1β expression, suggesting that MSU-induced LRP3 inflammasome activation was counteracted by DADS and DATS. Furthermore, DADS and DATS blocked oxidative stress, an upstream event for NLRP3 inflammasome activation, as evidenced by the fact that they scavenged reactive oxygen species (ROS) production. Taken together, our findings demonstrate that DADS and DATS suppressed NLRP3 inflammasome activation by inhibiting the ROS/NLRP3 pathway and that they have potential as treatments for NLRP3-dependent gouty arthritis.

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참고문헌 (Reference)

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