[6]-Gingerol Facilitates CXCL8 Secretion and ROS Production in Primary Human Neutrophils by Targeting the TRPV1 Channel

Mol Nutr Food Res. 2023 Feb;67(4):e2200434. doi: 10.1002/mnfr.202200434. Epub 2023 Jan 26.


Scope: Clarifying the function of sensory active TRP (transient receptor potential) channels in non-sensory tissue is of growing interest, especially with regard to food ingredients in nutritionally relevant concentrations. The study hypothesizes the TRPV1 agonist [6]-gingerol to facilitate cellular immune responses of primary human neutrophils, after treatment with 50 nM, a concentration that can be reached in the circulation after habitual dietary intake.

Methods and results: qRT-PCR analyses reveal a high abundancy of TRP channel RNA expression in the types of primary leukocytes investigated, namely neutrophils, monocytes, NK cells, T cells, and B cells. Incubation of neutrophils with 50 nM of the known TRPV1 ligand [6]-gingerol led to increased surface expression of CD11b, CD66b, and the fMLF receptor FPR1, as shown by flow cytometry. Upon subsequent stimulation with fMLF, the neutrophils display an about 30% (p < 0.05) increase in CXCL8 secretion as well as in ROS production. Pharmacological inhibition of TRPV1 by trans-tert-butylcyclohexanol abolishes the [6]-gingerol induced effects.

Conclusions: The TRPV1 channel is functionally expressed in human neutrophils. Activation of the channel with [6]-gingerol as a food-derived ligand in nutritionally relevant concentrations leads to an enhanced responsiveness in the cells towards activating stimuli, thereby facilitating a canonical cellular immune response in human neutrophils.

Keywords: food; ginger; immune system; immunomodulation; polymorphonuclear leukocytes (PMNs).

MeSH terms

  • Humans
  • Ligands
  • Neutrophils* / metabolism
  • Reactive Oxygen Species / metabolism
  • TRPV Cation Channels* / genetics


  • gingerol
  • Reactive Oxygen Species
  • TRPV Cation Channels
  • Ligands
  • TRPV1 protein, human