Activation of the TRPV1 channel via [6]-gingerol facilitates cellular immune responses in primary human neutrophils
Fri-P2-114
Presented by: Gaby Andersen
Clarifying the function of sensory active transient receptor potential (TRP) channels in non-sensory tissue is of growing interest, especially with regard to food ingredients in nutritionally relevant concentrations. The TRPV1 channel may probably be, by far, the most intensively investigated member of the TRP superfamily. However, its function in non-neuronal cell types like blood leukocytes is still under extensive investigation. Neutrophils are the most abundant leukocytes in human blood, accounting for 60-70% of all circulating white blood cells. They are the first immune cells which are recruited to the sites of infection. Besides direct defense mechanisms like ROS production, neutrophils contribute to subsequent immune responses via the release of various cytokines and chemokines.
The study hypothesized 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. RNA expression analyses revealed a high abundancy of TRP channel expression in the types of primary leukocyte 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 an increased surface expression of CD11b, CD66b, and the fMLF receptor FPR1. Upon subsequent stimulation with fMLF, the neutrophils displayed an about 30% (p<0.05) increase in CXCL8 secretion as well as in ROS production. Pharmacological inhibition of TRPV1 by trans-tert-butylcyclohexanol abolished the [6]-gingerol induced effects.
In conclusion, 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 of the cells towards activating stimuli, thereby facilitating a canonical cellular immune response of human neutrophils.
The study hypothesized 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. RNA expression analyses revealed a high abundancy of TRP channel expression in the types of primary leukocyte 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 an increased surface expression of CD11b, CD66b, and the fMLF receptor FPR1. Upon subsequent stimulation with fMLF, the neutrophils displayed an about 30% (p<0.05) increase in CXCL8 secretion as well as in ROS production. Pharmacological inhibition of TRPV1 by trans-tert-butylcyclohexanol abolished the [6]-gingerol induced effects.
In conclusion, 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 of the cells towards activating stimuli, thereby facilitating a canonical cellular immune response of human neutrophils.