Luteolin inhibits NLRP3 inflammasome activation via blocking ASC oligomerization |
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| Institution: | 1. Hard-tissue Biointerface Research Center, School of Dentistry, Chonnam National University, Gwangju, Republic of Korea;2. Department of Food and Nutrition, Chungbuk National University, Chundae-ro 1, Seowon-gu, Cheongju, Republic of Korea;3. Nutritional Immunology Laboratory, Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, Boston, Massachusetts, USA;1. College of Food Science and Engineering/Collaborative Innovation Center for Modern Grain Circulation and Safety/Key Laboratory of Grains and Oils Quality Control and Processing, Nanjing University of Finance and Economics, Nanjing, China;2. Basic Medical College, Nanjing University of Chinese Medicine, Nanjing, China;1. United States Department of Agriculture, Agricultural Research Service, Grand Forks Human Nutrition Research Center, Grand Forks, North Dakota;2. School of Public Health and Health Sciences, University of Massachusetts, Amherst, Massachusetts;3. School of Food and Agriculture, University of Maine, Orono, Maine;1. Laboratório de Genética Animal e Humana, Departamento de Genética, Ecologia e Evolução, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil;2. Center for Alcohol Research in Epigenetics, Department of Psychiatry, University of Illinois at Chicago, Chicago, IL, USA;3. Laboratório de Patologia Comparada, Departamento de Patologia Geral, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, Brazil;4. Departmento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil;5. Departamento de Nutrição, Escola de Enfermagem, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil; Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, Brazil;1. Department of Pharmacology, School of Pharmacy, China Pharmaceutical University, Nanjing, Jiangsu 210009, PR China;2. State Key Laboratory of Natural Medicines, Department of Physiology, China Pharmaceutical University, Nanjing, Jiangsu 210009, PR China;1. Cancer Biology Division, School of Biotechnology, Kalinga Institute of Industrial Technology (KIIT), Deemed to be University, Bhubaneswar-751024, Odisha, India;2. School of Medical Science and Technology, Indian Institute of Technology Kharagpur-721302, West Bengal, India;1. Department of Toxicology, School of Public Health, Zhejiang University, Zhejiang, Hangzhou 310058, China;2. Department of Gastroenterology, Second Affiliated Hospital, Zhejiang University School of Medicine, Zhejiang, Hangzhou 310009, China;3. Department of Gynecologic Oncology, Women''s Hospital, School of Medicine, Zhejiang University, Zhejiang, Hangzhou 310006, China;4. Department of Cardiology, Affiliated Hangzhou First People''s Hospital, Zhejiang University School of Medicine, Zhejiang, Hangzhou 310006, China;5. Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, 119077, Singapore;6. Central Laboratory, Affiliated Hangzhou First People''s Hospital, Zhejiang University School of Medicine, Zhejiang, Hangzhou 310006, China;7. Department of Toxicology, School of Public Health, Women''s Hospital, School of Medicine, Zhejiang University, Zhejiang, Hangzhou 310058, China |
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| Abstract: | The NLRP3 inflammasome is a caspase-1 containing multi-protein complex that controls the release of IL-1β and plays important roles in the innate immune response. Since NLRP3 inflammasome is implicated in the pathogenesis of a variety of diseases, it has become an increasingly interested target in developing therapies for multiple diseases. We reported the current study to determine how luteolin, a natural phenolic compound found in many vegetables and medicinal herbs, would modulate NLRP3 inflammasome in both the in vivo and in vitro settings. First, we found that a high-fat diet upregulated mRNA expression of NLRP3 inflammasome components Asc and Casp1 in adipose tissue of ovariectomized mice, which were greatly reduced by dietary supplementation with luteolin. Of note, Asc and Casp1 expression in adipose tissue correlated with mRNA levels of Adgre1 encoding F4/80, an established marker for mature macrophages. We also demonstrated that luteolin inhibited NLRP3 inflammasome-derived caspase-1 activation and IL-1β secretion in J774A.1 macrophages upon diverse stimuli including ATP, nigericin, or silica crystals. Luteolin inhibited the activation step of NLRP3 inflammasome by interfering with ASC oligomerization. Taken together, these findings suggest that luteolin supplementation may suppress NLRP3 induction and activation process and thus potentially would be protective against NLRP3-mediated inflammatory diseases. |
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