The ketone body acetoacetate activates human neutrophils through FFAR2
文献类型：期刊论文
| 作者 | Martensson, Jonas2; Bjorkman, Lena2; Lind, Simon2; Viklund, Moa Bjerhem2; Zhang, Linjie3,4; Gutierrez, Saray1; Dahlgren, Claes2; Sundqvist, Martina2; Xie, Xin3,4 ; Forsman, Huamei2,5
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| 刊名 | JOURNAL OF LEUKOCYTE BIOLOGY
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| 出版日期 | 2023-06-01 |
| 卷号 | 113期号:6页码:577-587 |
| 关键词 | acetoacetate FFAR2 G-protein coupled receptor ketone body neutrophil |
| ISSN号 | 0741-5400 |
| DOI | 10.1093/jleuko/qiad035 |
| 通讯作者 | Forsman, Huamei(huamei.forsman@gu.se) |
| 英文摘要 | Neutrophils express many surface receptors that sense environmental changes. One such sensor is FFAR2 (free fatty acid receptor 2), a receptor that detects gut microbiota-derived short-chain fatty acids. As such, FFAR2 has been regarded as a molecular link between metabolism and inflammation. Our recent studies on FFAR2, using its endogenous agonist propionate in combination with allosteric modulators, have identified several novel aspects of FFAR2 regulation. A recent study has also identified the ketone body acetoacetate as an endogenous ligand for mouse FFAR2. Whether human FFAR2 also recognizes acetoacetate and how this recognition modulates human neutrophil functions has not been investigated. In this study, we found that acetoacetate can induce a decrease of cAMP and translocation of beta-arrestin in cells overexpressing FFAR2. In addition, we show that similar to propionate, FFAR2-specific allosteric modulators enhance acetoacetate-induced transient rise in cytosolic calcium, production of reactive oxygen species, and cell migration in human neutrophils. In summary, we demonstrate that human neutrophils recognize the ketone body acetoacetate through FFAR2. Thus, our data further highlight the key role of FFAR2 in inflammation and metabolism. |
| WOS关键词 | NLRP3 INFLAMMASOME ; RECEPTORS ; METABOLISM ; BODIES ; RECRUITMENT ; HEALTH ; ROLES ; ALPHA ; GPR43 |
| 资助项目 | Swedish Research Council ; Swedish government under the ALF-agreement ; Rune and Ulla Amlov Foundation ; Gothenburg Society of Medicine ; Clas Groschinskys Memorial Fund[MS M21146] ; Ake Wiberg Foundation ; Sahlgrenska International Starting Grant ; Magnus Bergwall Foundation[MS 2021-04110] ; Ingabritt and Arne Lundberg Foundation |
| WOS研究方向 | Cell Biology ; Hematology ; Immunology |
| 语种 | 英语 |
| WOS记录号 | WOS:001000297300005 |
| 出版者 | OXFORD UNIV PRESS |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/306227]  |
| 专题 | 中国科学院上海药物研究所 |
| 通讯作者 | Forsman, Huamei |
| 作者单位 | 1.BioPharmaceut R&D, Biosci Cardiovasc Res & Early Dev, Cardiovasc Renal & Metab CVRM, Pepparedsleden 1, S-43183 Molndal, Sweden 2.Univ Gothenburg, Inst Med, Sahlgrenska Acad, Dept Rheumatol & Inflammat Res, Guldhedsgatan 10A, S-41346 Gothenburg, Sweden 3.Chinese Acad Sci, Shanghai Inst Mat Med, Natl Ctr Drug Screening, CAS Key Lab Receptor Res, 555 Zuchongzhi Rd, Shanghai 201203, Peoples R China 4.Univ Chinese Acad Sci, 19A Yuquan Rd, Beijing 100049, Peoples R China 5.Dept Rheumatol & Inflammat Res, Guldhedsgatan 10A, S-41346 Gothenburg, Sweden |
| 推荐引用方式 GB/T 7714 | Martensson, Jonas,Bjorkman, Lena,Lind, Simon,et al. The ketone body acetoacetate activates human neutrophils through FFAR2[J]. JOURNAL OF LEUKOCYTE BIOLOGY,2023,113(6):577-587. |
| APA | Martensson, Jonas.,Bjorkman, Lena.,Lind, Simon.,Viklund, Moa Bjerhem.,Zhang, Linjie.,...&Forsman, Huamei.(2023).The ketone body acetoacetate activates human neutrophils through FFAR2.JOURNAL OF LEUKOCYTE BIOLOGY,113(6),577-587. |
| MLA | Martensson, Jonas,et al."The ketone body acetoacetate activates human neutrophils through FFAR2".JOURNAL OF LEUKOCYTE BIOLOGY 113.6(2023):577-587. |
入库方式： OAI收割
来源：上海药物研究所
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