2. Academic Validation
  3. TLR-2-mediated metabolic reprogramming participates in polyene phosphatidylcholine-mediated inhibition of M1 macrophage polarization

TLR-2-mediated metabolic reprogramming participates in polyene phosphatidylcholine-mediated inhibition of M1 macrophage polarization

  • Immunol Res. 2020 Feb;68(1):28-38. doi: 10.1007/s12026-020-09125-9.
Ting-Ting Feng 1,  Xiao-Ying Yang 2,  Shan-Shan Hao 2,  Fen-Fen Sun 2,  Ye Huang 1,  Qi-Si Lin 3,  Wei Pan 4 5
Affiliations

Affiliations

  • 1 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.
  • 2 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.
  • 3 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.
  • 4 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.
  • 5 JOINN Laboratories (Suzhou), Suzhou, 215421, Jiangsu Province, People's Republic of China. panwei525@126.com.
PMID: 32248343 DOI: 10.1007/s12026-020-09125-9
Abstract

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-α, 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-γ) and GW6471 (an inhibitor of PPAR-α) 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-α 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.

Keywords

Macrophage polarization; Metabolic reprogramming; Polyene phosphatidylcholine; TLR-2.

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