PMID- 32248343
OWN - NLM
STAT- MEDLINE
DCOM- 20201228
LR  - 20201228
IS  - 1559-0755 (Electronic)
IS  - 0257-277X (Linking)
VI  - 68
IP  - 1
DP  - 2020 Feb
TI  - TLR-2-mediated metabolic reprogramming participates in polyene 
      phosphatidylcholine-mediated inhibition of M1 macrophage polarization.
PG  - 28-38
LID - 10.1007/s12026-020-09125-9 [doi]
AB  - This study aimed to investigate whether the classic hepatoprotective drug polyene 
      phosphatidylcholine (PPC) regulates macrophage polarization and explores the 
      potential role of TLR-2 in this process. In RAW264.7 macrophages and murine bone 
      marrow-derived macrophages (BMDMs) stimulated by lipopolysaccharide (LPS), PPC 
      significantly inhibited the production of IL-6, TNF-alpha, and the mRNA expression of 
      M1-type macrophage markers. Consistently, PPC reduced the mRNA expression of 
      several key enzymes in the pathways of glycolysis and lipid synthesis while 
      increasing the expression of key enzymes associated with lipid oxidation. 
      Moreover, blocking the glycolytic pathway using 2-deoxy-D-glucose (2-DG) 
      significantly enhanced the anti-inflammatory effect of PPC. However, inhibition 
      of lipid oxidation using GW9662 (an inhibitor of PPAR-gamma) and GW6471 (an inhibitor 
      of PPAR-alpha) abolished the anti-inflammatory effect of PPC. Interestingly, TLR-2 
      expression in macrophages was significantly downregulated after exposure to PPC. 
      Moreover, pre-activation of TLR-2 hampered the anti-inflammatory effect of PPC. 
      In addition, PPC did not inhibit the secretion of IL-6 and TNF-alpha in TLR-2(-/-) 
      BMDMs that were activated by LPS. This was consistent with the increased 
      expression of M1 markers and glycolytic and lipid synthesis enzymes but decreased 
      lipid oxidation-related enzymes. These results showed that PPC inhibits the 
      differentiation of M1-type macrophages, which was most likely related to 
      TLR-2-mediated metabolic reprogramming.
FAU - Feng, Ting-Ting
AU  - Feng TT
AD  - Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical 
      University, Tongshan Road 209, Xuzhou, 221004, Jiangsu Province, People's 
      Republic of China.
FAU - Yang, Xiao-Ying
AU  - Yang XY
AD  - Jiangsu Key Laboratory of Immunity and Metabolism, Department of Pathogenic 
      Biology and Immunology, Xuzhou Medical University, Tongshan Road 209, Xuzhou, 
      221004, Jiangsu Province, People's Republic of China.
FAU - Hao, Shan-Shan
AU  - Hao SS
AD  - Jiangsu Key Laboratory of Immunity and Metabolism, Department of Pathogenic 
      Biology and Immunology, Xuzhou Medical University, Tongshan Road 209, Xuzhou, 
      221004, Jiangsu Province, People's Republic of China.
FAU - Sun, Fen-Fen
AU  - Sun FF
AD  - Jiangsu Key Laboratory of Immunity and Metabolism, Department of Pathogenic 
      Biology and Immunology, Xuzhou Medical University, Tongshan Road 209, Xuzhou, 
      221004, Jiangsu Province, People's Republic of China.
FAU - Huang, Ye
AU  - Huang Y
AD  - Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical 
      University, Tongshan Road 209, Xuzhou, 221004, Jiangsu Province, People's 
      Republic of China.
FAU - Lin, Qi-Si
AU  - Lin QS
AD  - Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical 
      University, Tongshan Road 209, Xuzhou, 221004, Jiangsu Province, People's 
      Republic of China. qslin074@126.com.
FAU - Pan, Wei
AU  - Pan W
AD  - Jiangsu Key Laboratory of Immunity and Metabolism, Department of Pathogenic 
      Biology and Immunology, Xuzhou Medical University, Tongshan Road 209, Xuzhou, 
      221004, Jiangsu Province, People's Republic of China. panwei525@126.com.
AD  - JOINN Laboratories (Suzhou), Suzhou, 215421, Jiangsu Province, People's Republic 
      of China. panwei525@126.com.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Immunol Res
JT  - Immunologic research
JID - 8611087
RN  - 0 (Anti-Inflammatory Agents)
RN  - 0 (Interleukin-6)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (Phosphatidylcholines)
RN  - 0 (Tlr2 protein, mouse)
RN  - 0 (Toll-Like Receptor 2)
RN  - 0 (Tumor Necrosis Factor-alpha)
SB  - IM
MH  - Animals
MH  - Anti-Inflammatory Agents/*pharmacology
MH  - Cell Differentiation
MH  - Cellular Reprogramming
MH  - Female
MH  - Interleukin-6/metabolism
MH  - Lipid Peroxidation
MH  - Lipopolysaccharides/immunology
MH  - Macrophages/*physiology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Phosphatidylcholines/*pharmacology
MH  - RAW 264.7 Cells
MH  - Signal Transduction
MH  - Th1 Cells/immunology
MH  - Toll-Like Receptor 2/genetics/*metabolism
MH  - Tumor Necrosis Factor-alpha/metabolism
OTO - NOTNLM
OT  - Macrophage polarization
OT  - Metabolic reprogramming
OT  - Polyene phosphatidylcholine
OT  - TLR-2
EDAT- 2020/04/06 06:00
MHDA- 2020/12/29 06:00
CRDT- 2020/04/06 06:00
PHST- 2020/04/06 06:00 [pubmed]
PHST- 2020/12/29 06:00 [medline]
PHST- 2020/04/06 06:00 [entrez]
AID - 10.1007/s12026-020-09125-9 [pii]
AID - 10.1007/s12026-020-09125-9 [doi]
PST - ppublish
SO  - Immunol Res. 2020 Feb;68(1):28-38. doi: 10.1007/s12026-020-09125-9.