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Front Immunol. 2018 Nov 20;9:2670. doi: 10.3389/fimmu.2018.02670. eCollection 2018.

Betaine Inhibits Interleukin-1β Production and Release: Potential Mechanisms.

Xia Y1,2,3, Chen S2,3, Zhu G4, Huang R3, Yin Y1,3,5, Ren W1,4.

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Guangdong Provincial Key Laboratory of Animal Nutrition Control, Institute of Subtropical Animal Nutrition and Feed, College of Animal Science, South China Agricultural University, Guangzhou, China.
University of Chinese Academy of Sciences, Beijing, China.
Laboratory of Animal Nutrition and Health and Key Laboratory of Agro-Ecology, Institute of Subtropical Agriculture, Chinese Academy of Sciences, Changsha, China.
Jiangsu Co-Innovation Center for Important Animal Infectious Diseases and Zoo Noses, Joint International Research Laboratory of Agriculture and Agri-Product Safety of Ministry of Education of China, College of Veterinary Medicine, Yangzhou University, Yangzhou, China.
Academics Working Station at The First Affiliated Hospital, Changsha Medical University, Changsha, China.


Betaine is a critical nutrient for mammal health, and has been found to alleviate inflammation by lowering interleukin (IL)-1β secretion; however, the underlying mechanisms by which betaine inhibits IL-1β secretion remain to be uncovered. In this review, we summarize the current understanding about the mechanisms of betaine in IL-1β production and release. For IL-1β production, betaine affects canonical and non-canonical inflammasome-mediated processing of IL-1β through signaling pathways, such as NF-κB, NLRP3 and caspase-8/11. For IL-1β release, betaine inhibits IL-1β release through blocking the exocytosis of IL-1β-containing secretory lysosomes, reducing the shedding of IL-1β-containing plasma membrane microvesicles, suppressing the exocytosis of IL-1β-containing exosomes, and attenuating the passive efflux of IL-1β across hyperpermeable plasma membrane during pyroptotic cell death, which are associated with ERK1/2/PLA2 and caspase-8/A-SMase signaling pathways. Collectively, this review highlights the anti-inflammatory property of betaine by inhibiting the production and release of IL-1β, and indicates the potential application of betaine supplementation as an adjuvant therapy in various inflammatory diseases associating with IL-1β secretion.


IL-1β; betaine; caspase-8; inflammasome; inflammation

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