Magnesium-enriched deep-sea water inhibits NLRP3 inflammasome activation and dampens inflammation
Hsueh-Hsiao Wang,
Chi-Ruei Huang,
Hsin-Chung Lin,
Hsin-An Lin,
Yu-Jen Chen,
Kuen-Jou Tsai,
Chieh-Tien Shih,
Kuo-Yang Huang,
David M. Ojcius,
Ming-Hang Tsai,
Kuang-Wen Tseng,
Lih-Chyang Chen
Affiliations
Hsueh-Hsiao Wang
Department of Medicine, MacKay Medical College, New Taipei City, 252, Taiwan
Chi-Ruei Huang
Master Program in Biomedicine, College of Science and Engineering, National Taitung University, Taitung County, China; Biomedicine, Agriculture and Food Sciences Research Center, College of Science and Engineering, National Taitung University, Taitung County, China
Hsin-Chung Lin
Graduate Institute of Pathology and Parasitology, National Defense Medical Center, Taipei City, 114, Taiwan; Division of Clinical Pathology, Department of Pathology, Tri-Service General Hospital, National Defense Medical Center, Taipei City, 114, Taiwan
Hsin-An Lin
Division of Infection, Department of Medicine, Tri-Service General Hospital SongShan Branch, National Defense Medical Center, Taipei City, 105, Taiwan; Department of Health Promotion and Health Education, National Taiwan Normal University, Taipei City, 106, Taiwan
Yu-Jen Chen
Department of Medicine, MacKay Medical College, New Taipei City, 252, Taiwan; Department of Medical Research, MacKay Memorial Hospital, New Taipei City, 251, Taiwan; Department of Radiation Oncology, MacKay Memorial Hospital, Taipei, 104, Taiwan; Department of Artificial Intelligence and Medical Application, MacKay Junior College of Medicine, Nursing and Management, Taipei, 112, Taiwan; Department of Medical Research, China Medical University Hospital, Taichung, 404, Taiwan
Kuen-Jou Tsai
Department of Laboratory Medicine, MacKay Memorial Hospital, Taipei, 104, Taiwan; Department of Nursing, MacKay Medical College, New Taipei City, 252, Taiwan
Chieh-Tien Shih
Department of Medicine, MacKay Medical College, New Taipei City, 252, Taiwan
Kuo-Yang Huang
Graduate Institute of Pathology and Parasitology, National Defense Medical Center, Taipei City, 114, Taiwan
David M. Ojcius
Department of Biomedical Sciences, University of the Pacific, Arthur Dugoni School of Dentistry, San Francisco, CA, 94103, USA
Ming-Hang Tsai
Department of Medicine, Tri-Service General Hospital SongShan Branch, National Defense Medical Center, Taipei City, 105, Taiwan
Kuang-Wen Tseng
Department of Medicine, MacKay Medical College, New Taipei City, 252, Taiwan
Lih-Chyang Chen
Department of Medicine, MacKay Medical College, New Taipei City, 252, Taiwan; Corresponding author.
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 Mg2+ could potentially be beneficial in modulating NLRP3 inflammasome-associated diseases.