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Transient Receptor Potential Ankyrin 1 Contributes to Lysophosphatidylcholine-Induced Intracellular Calcium Regulation and THP-1-Derived Macrophage Activation

Abstract

Lysophosphatidylcholine (LPC) is a major atherogenic lipid that stimulates an increase in mitochondrial reactive oxygen species (mtROS) and the release of cytokines under inflammasome activation. However, the potential receptors of LPC in macrophages are poorly understood. Members of the transient receptor potential (TRP) channel superfamily, which is crucially involved in transducing environmental irritant stimuli into nociceptor activity, are potential receptors of LPC. In this study, we investigated whether LPC can induce the activation of transient receptor potential ankyrin 1 (TRPA1), a member of the TRP superfamily. The functional expression of TRPA1 was first detected by quantitative real-time polymerase chain reaction (qRT-PCR), western blotting and calcium imaging in human acute monocytic leukemia cell line (THP-1)-derived macrophages. The mechanism by which LPC induces the activation of macrophages through TRPA1 was verified by cytoplasmic and mitochondrial calcium imaging, mtROS detection, a JC-1 assay, enzyme-linked immunosorbent assay, the CCK-8 assay and the lactate dehydrogenase (LDH) cytotoxic assay. LPC induced the activation of THP-1-derived macrophages via calcium influx, and this activation was suppressed by potent and selective inhibitors of TRPA1. These results indicated that TRPA1 can mediate mtROS generation, mitochondrial membrane depolarization, the secretion of IL-1β and cytotoxicity through cellular and mitochondrial Ca2+ influx in LPC-treated THP-1-derived macrophages. Therefore, the inhibition of TRPA1 may protect THP-1-derived macrophages against LPC-induced injury.

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Acknowledgements

This work was supported by the Frontier Research Program of Guangzhou Regenerative Medicine and Health Guangdong Laboratory, Grant No. 2018GZR110105020 and the Guangdong Provincial Natural Science Foundation (2017A030313757 and 2016A030313170), the National Natural Science Foundation of China (31671211). The kind gift of the THP-1 cell line from Dr. Peng Li, Guangzhou Institute of Biomedicine and Health, Chinese Academy of Sciences, China, is deeply appreciated.

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Correspondence to Zhiyuan Li.

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Tian, C., Huang, R., Tang, F. et al. Transient Receptor Potential Ankyrin 1 Contributes to Lysophosphatidylcholine-Induced Intracellular Calcium Regulation and THP-1-Derived Macrophage Activation. J Membrane Biol 253, 43–55 (2020) doi:10.1007/s00232-019-00104-2

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Keywords

  • TRPA1
  • LPC
  • Reactive oxygen species
  • Mitochondria
  • Macrophage
  • Calcium