Wang Hsueh-Hsiao, Huang Chi-Ruei, Lin Hsin-Chung, Lin Hsin-An, Chen Yu-Jen, Tsai Kuen-Jou, Shih Chieh-Tien, Huang Kuo-Yang, Ojcius David M, Tsai Ming-Hang, Tseng Kuang-Wen, Chen Lih-Chyang
Department of Medicine, MacKay Medical College, New Taipei City, 252, Taiwan.
Master Program in Biomedicine, College of Science and Engineering, National Taitung University, Taitung County, China.
Heliyon. 2024 Jul 23;10(15):e35136. doi: 10.1016/j.heliyon.2024.e35136. eCollection 2024 Aug 15.
The NLRP3 inflammasome is an essential component of the innate immune system, but excessive activation can lead to inflammatory diseases. Ion fluxes across the plasma membrane or from intracellular stores are known to regulate NLRP3 inflammasome activation. Deep-sea water (DSW) contains high concentrations of many mineral ions, which could potentially influence NLRP3 inflammasome activation. However, the impact of DSW on NLRP3 inflammasome activation has not been investigated. Here, we demonstrated that DSW with water hardness levels up to 500 mg/L did not affect cell viability or the expression of NLRP3 inflammasome components in macrophages derived from THP-1 cells. However, the DSW significantly inhibited IL-1β secretion and caspase-1 activation in response to NLRP3 activators such as nigericin, ATP, or monosodium urate (MSU) crystals. Mechanically, it was discovered that the presence of 5 mM magnesium ions (Mg2), equivalent to the Mg2 concentration found in the DSW with a water hardness of 500 mg/L, inhibits NLRP3 inflammasome activation. This indicates that Mg2 contributes to the mechanism by which DSW mitigates NLRP3 inflammasome activation. Moreover, DSW administration effectively lessens MSU-triggered peritonitis in mice, a commonly used model for examining the impacts of NLRP3 inflammasome activation. These results show that DSW enriched with Mg could potentially be beneficial in modulating NLRP3 inflammasome-associated diseases.
NLRP3炎性小体是天然免疫系统的重要组成部分，但过度激活会导致炎症性疾病。已知跨质膜或从细胞内储存库的离子通量可调节NLRP3炎性小体的激活。深海水（DSW）含有高浓度的多种矿质离子，这可能会影响NLRP3炎性小体的激活。然而，DSW对NLRP3炎性小体激活的影响尚未得到研究。在此，我们证明水硬度高达500mg/L的DSW不会影响源自THP-1细胞的巨噬细胞的细胞活力或NLRP3炎性小体成分的表达。然而，DSW显著抑制了对NLRP3激活剂（如尼日利亚菌素、ATP或尿酸钠（MSU）晶体）的反应中IL-1β的分泌和caspase-1的激活。从机制上讲，发现5mM镁离子（Mg2+）的存在，相当于水硬度为500mg/L的DSW中发现的Mg2+浓度，可抑制NLRP3炎性小体的激活。这表明Mg2+有助于DSW减轻NLRP3炎性小体激活的机制。此外，给予DSW可有效减轻MSU引发的小鼠腹膜炎，这是一种常用的用于研究NLRP3炎性小体激活影响的模型。这些结果表明，富含Mg的DSW可能对调节NLRP3炎性小体相关疾病有益。
