Role of TRPM8 in negative regulation of inflammatory factors by menthol
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1.Institute of Medical Laboratory Animal Science, Chinese Academy of Medical Sciences (CAMS). Comparative Medicine Center, Peking Union Medical College (PUMC). NHC Key Laboratory of Human Disease Comparative Medicine. Beijing Engineering Research Center for Experimental Animal Models of Human Critical Diseases, Beijing 100021, China. 2. MOE Key Laboratory of Protein Sciences. Laboratory of Molecular Pharmacology and Pharmaceutical Sciences, School of Life Sciences and School of Medicine, Tsinghua University, Beijing 100084

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R-33

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    Abstract:

    Objective To elucidate the molecular mechanism of the negative regulation of inflammatory factors by menthol through transient receptor potential melastatin 8 (TRPM8). Methods In an in vivo experiment, we detected expression of the cold-sensitive receptor TRPM8, nuclear transcription factor NF-κB, and inflammatory factor TNF-α after intravenous injection of (-)-menthol. In an in vitro experiment, we examined the effect of menthol on TRPM8, NF-κB, and TNF-α expression in PC12 cells. Finally, we examined the negative relationship between TRPM8 and TNF-α in PC12 cells (TRPM8 knockdown). Results The three main findings of this study are as follows. First, after intravenous injection of menthol, expression of the cold-sensitive receptor TRPM8 in the hypothalamus of mice was activated, and expression of the nuclear transcription factor NF-κB and inflammatory factor TNF-α was inhibited. Second, in the neuron-like PC12 cells, menthol activated TRPM8 expression and inhibited NF-κB and TNF-α. Third, in PC12 cells with TRPM8 knockdown, menthol showed no significant effect on TRPM8 expression; in contrast, TNF-α expression was activated. Conclusions The negative regulation of inflammatory factors by menthol depends on the activation of TRPM8 expression.

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History
  • Received:October 28,2020
  • Online: August 03,2021
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