PMID- 38442142
OWN - NLM
STAT- MEDLINE
DCOM- 20240307
LR  - 20240317
IS  - 2050-084X (Electronic)
IS  - 2050-084X (Linking)
VI  - 12
DP  - 2024 Mar 5
TI  - Leucine alleviates cytokine storm syndrome by regulating macrophage polarization 
      via the mTORC1/LXRalpha signaling pathway.
LID - 10.7554/eLife.89750 [doi]
LID - RP89750
AB  - Cytokine storms are associated with severe pathological damage and death in some 
      diseases. Excessive activation of M1 macrophages and the subsequent secretion of 
      pro-inflammatory cytokines are a major cause of cytokine storms. Therefore, 
      promoting the polarization of M2 macrophages to restore immune balance is a 
      promising therapeutic strategy for treating cytokine storm syndrome (CSS). This 
      study was aimed at investigating the potential protective effects of leucine on 
      lipopolysaccharide (LPS)-induced CSS in mice and exploring the underlying 
      mechanisms. CSS was induced by LPS administration in mice, which were 
      concurrently administered leucine orally. In vitro, bone marrow derived 
      macrophages (BMDMs) were polarized to M1 and M2 phenotypes with LPS and 
      interleukin-4 (IL-4), respectively, and treated with leucine. Leucine decreased 
      mortality in mice treated with lethal doses of LPS. Specifically, leucine 
      decreased M1 polarization and promoted M2 polarization, thus diminishing 
      pro-inflammatory cytokine levels and ameliorating CSS in mice. Further studies 
      revealed that leucine-induced macrophage polarization through the mechanistic 
      target of rapamycin complex 1 (mTORC1)/liver X receptor alpha (LXRalpha) pathway, which 
      synergistically enhanced the expression of the IL-4-induced M2 marker Arg1 and 
      subsequent M2 polarization. In summary, this study revealed that leucine 
      ameliorates CSS in LPS mice by promoting M2 polarization through the 
      mTORC1/LXRalpha/Arg1 signaling pathway. Our findings indicate that a fundamental link 
      between metabolism and immunity contributes to the resolution of inflammation and 
      the repair of damaged tissues.
CI  - (c) 2023, Yan, Liu, Li et al.
FAU - Yan, Hui
AU  - Yan H
AUID- ORCID: 0000-0001-7476-3914
AD  - Key Laboratory of Animal Disease Resistance Nutrition of China Ministry of 
      Education, Key Laboratory of Animal Disease resistant Nutrition and Feed of China 
      Ministry of Agriculture and Rural Affairs, Key Laboratory of Animal Disease 
      resistant Nutrition of Sichuan Province, Animal Nutrition Institute, Sichuan 
      Agricultural University, Chengdu, China.
FAU - Liu, Yao
AU  - Liu Y
AUID- ORCID: 0000-0001-5141-3161
AD  - Key Laboratory of Animal Disease Resistance Nutrition of China Ministry of 
      Education, Key Laboratory of Animal Disease resistant Nutrition and Feed of China 
      Ministry of Agriculture and Rural Affairs, Key Laboratory of Animal Disease 
      resistant Nutrition of Sichuan Province, Animal Nutrition Institute, Sichuan 
      Agricultural University, Chengdu, China.
FAU - Li, Xipeng
AU  - Li X
AD  - Key Laboratory of Animal Disease Resistance Nutrition of China Ministry of 
      Education, Key Laboratory of Animal Disease resistant Nutrition and Feed of China 
      Ministry of Agriculture and Rural Affairs, Key Laboratory of Animal Disease 
      resistant Nutrition of Sichuan Province, Animal Nutrition Institute, Sichuan 
      Agricultural University, Chengdu, China.
FAU - Yu, Bing
AU  - Yu B
AD  - Key Laboratory of Animal Disease Resistance Nutrition of China Ministry of 
      Education, Key Laboratory of Animal Disease resistant Nutrition and Feed of China 
      Ministry of Agriculture and Rural Affairs, Key Laboratory of Animal Disease 
      resistant Nutrition of Sichuan Province, Animal Nutrition Institute, Sichuan 
      Agricultural University, Chengdu, China.
FAU - He, Jun
AU  - He J
AD  - Key Laboratory of Animal Disease Resistance Nutrition of China Ministry of 
      Education, Key Laboratory of Animal Disease resistant Nutrition and Feed of China 
      Ministry of Agriculture and Rural Affairs, Key Laboratory of Animal Disease 
      resistant Nutrition of Sichuan Province, Animal Nutrition Institute, Sichuan 
      Agricultural University, Chengdu, China.
FAU - Mao, Xiangbing
AU  - Mao X
AD  - Key Laboratory of Animal Disease Resistance Nutrition of China Ministry of 
      Education, Key Laboratory of Animal Disease resistant Nutrition and Feed of China 
      Ministry of Agriculture and Rural Affairs, Key Laboratory of Animal Disease 
      resistant Nutrition of Sichuan Province, Animal Nutrition Institute, Sichuan 
      Agricultural University, Chengdu, China.
FAU - Yu, Jie
AU  - Yu J
AD  - Key Laboratory of Animal Disease Resistance Nutrition of China Ministry of 
      Education, Key Laboratory of Animal Disease resistant Nutrition and Feed of China 
      Ministry of Agriculture and Rural Affairs, Key Laboratory of Animal Disease 
      resistant Nutrition of Sichuan Province, Animal Nutrition Institute, Sichuan 
      Agricultural University, Chengdu, China.
FAU - Huang, Zhiqing
AU  - Huang Z
AUID- ORCID: 0000-0001-5092-9297
AD  - Key Laboratory of Animal Disease Resistance Nutrition of China Ministry of 
      Education, Key Laboratory of Animal Disease resistant Nutrition and Feed of China 
      Ministry of Agriculture and Rural Affairs, Key Laboratory of Animal Disease 
      resistant Nutrition of Sichuan Province, Animal Nutrition Institute, Sichuan 
      Agricultural University, Chengdu, China.
FAU - Luo, Yuheng
AU  - Luo Y
AD  - Key Laboratory of Animal Disease Resistance Nutrition of China Ministry of 
      Education, Key Laboratory of Animal Disease resistant Nutrition and Feed of China 
      Ministry of Agriculture and Rural Affairs, Key Laboratory of Animal Disease 
      resistant Nutrition of Sichuan Province, Animal Nutrition Institute, Sichuan 
      Agricultural University, Chengdu, China.
FAU - Luo, Junqiu
AU  - Luo J
AD  - Key Laboratory of Animal Disease Resistance Nutrition of China Ministry of 
      Education, Key Laboratory of Animal Disease resistant Nutrition and Feed of China 
      Ministry of Agriculture and Rural Affairs, Key Laboratory of Animal Disease 
      resistant Nutrition of Sichuan Province, Animal Nutrition Institute, Sichuan 
      Agricultural University, Chengdu, China.
FAU - Wu, Aimin
AU  - Wu A
AD  - Key Laboratory of Animal Disease Resistance Nutrition of China Ministry of 
      Education, Key Laboratory of Animal Disease resistant Nutrition and Feed of China 
      Ministry of Agriculture and Rural Affairs, Key Laboratory of Animal Disease 
      resistant Nutrition of Sichuan Province, Animal Nutrition Institute, Sichuan 
      Agricultural University, Chengdu, China.
FAU - Chen, Daiwen
AU  - Chen D
AUID- ORCID: 0000-0002-8351-7421
AD  - Key Laboratory of Animal Disease Resistance Nutrition of China Ministry of 
      Education, Key Laboratory of Animal Disease resistant Nutrition and Feed of China 
      Ministry of Agriculture and Rural Affairs, Key Laboratory of Animal Disease 
      resistant Nutrition of Sichuan Province, Animal Nutrition Institute, Sichuan 
      Agricultural University, Chengdu, China.
LA  - eng
GR  - 2023YFD1300803/National Key Research and Development Program of China/
GR  - U22A20513/Natural Science Foundation of China/
GR  - 2021ZDZX0009/Science and Technology Program of Sichuan/
GR  - 2021YJ0195/Science and Technology Program of Sichuan/
PT  - Journal Article
DEP - 20240305
PL  - England
TA  - Elife
JT  - eLife
JID - 101579614
RN  - 0 (Liver X Receptors)
RN  - 207137-56-2 (Interleukin-4)
RN  - GMW67QNF9C (Leucine)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (Cytokines)
RN  - EC 2.7.11.1 (Mechanistic Target of Rapamycin Complex 1)
SB  - IM
UOF - doi: 10.1101/2023.06.21.546014
UOF - doi: 10.7554/eLife.89750.1
UOF - doi: 10.7554/eLife.89750.2
MH  - Animals
MH  - Mice
MH  - *Cytokine Release Syndrome
MH  - Liver X Receptors
MH  - *Interleukin-4
MH  - Leucine/pharmacology
MH  - Lipopolysaccharides
MH  - Cytokines
MH  - Signal Transduction
MH  - Macrophages
MH  - Mechanistic Target of Rapamycin Complex 1
PMC - PMC10942637
OTO - NOTNLM
OT  - BMDM
OT  - c57bl6
OT  - immunology
OT  - inflammation
OT  - macrophages
OT  - mouse
COIS- HY, YL, XL, BY, JH, XM, JY, ZH, YL, JL, AW, DC No competing interests declared
EDAT- 2024/03/05 18:42
MHDA- 2024/03/07 06:43
PMCR- 2024/03/05
CRDT- 2024/03/05 13:53
PHST- 2024/03/07 06:43 [medline]
PHST- 2024/03/05 18:42 [pubmed]
PHST- 2024/03/05 13:53 [entrez]
PHST- 2024/03/05 00:00 [pmc-release]
AID - 89750 [pii]
AID - 10.7554/eLife.89750 [doi]
PST - epublish
SO  - Elife. 2024 Mar 5;12:RP89750. doi: 10.7554/eLife.89750.