Aspartate Metabolism Facilitates IL-1β Production in Inflammatory Macrophages

被引：47

作者：

Wang, Hao ^{[1
]}

Zheng, Xueyue ^{[1
]}

Liu, Bingnan ^{[1
]}

Xia, Yaoyao ^{[1
]}

Xin, Zhongquan ^{[1
]}

Deng, Baichuan ^{[1
]}

He, Liuqin ^{[2
,3
]}

Deng, Jinping ^{[1
]}

Ren, Wenkai ^{[1
]}

机构：

[1] South China Agr Univ, Coll Anim Sci, Natl Engn Res Ctr Breeding Swine Ind, State Key Lab Conservat & Utilizat Subtrop Agro B, Guangzhou, Peoples R China

[2] Hunan Normal Univ, Coll Life Sci, Hunan Prov Key Lab Anim Intestinal Funct & Regula, Lab Anim Nutr & Human Hlth, Changsha, Peoples R China

[3] Chinese Acad Sci, Inst Subtrop Agr, Changsha, Peoples R China

来源：

FRONTIERS IN IMMUNOLOGY | 2021年 / 12卷

基金：

中国国家自然科学基金;

关键词：

asparagine; aspartate; HIF-1; alpha; inflammasome; macrophage;

D O I：

10.3389/fimmu.2021.753092

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

Increasing evidence support that cellular amino acid metabolism shapes the fate of immune cells; however, whether aspartate metabolism dictates macrophage function is still enigmatic. Here, we found that the metabolites in aspartate metabolism are depleted in lipopolysaccharide (LPS) plus interferon gamma (IFN-gamma)-stimulated macrophages. Aspartate promotes interleukin-1 beta ( IL- 1 beta) secretion in M1 macrophages. Mechanistically, aspartate boosts the activation of hypoxia-inducible factor-1 alpha (HIF-1 alpha) and inflammasome and increases the levels of metabolites in aspartate metabolism, such as asparagine. Interestingly, asparagine also accelerates the activation of cellular signaling pathways and promotes the production of inflammatory cytokines from macrophages. Moreover, aspartate supplementation augments the macrophage-mediated inflammatory responses in mice and piglets. These results uncover a previously uncharacterized role for aspartate metabolism in directing M1 macrophage polarization.

引用

页数：13

共 61 条

[51] Redox Remodeling Allows and Controls B-Cell Activation and Differentiation [J].