Abstract
Introduction.
Interleukin-4 (IL-4) is a key mediator of Th2 inflammation in asthma and is capable of profoundly altering the receptor profile of monocytes. However, data on the effect of IL-4 on the expression of the bitter taste receptor family (TAS2R) in circulating immune cells are currently lacking.
Aim.
To characterize the effect of recombinant IL-4 at physiologically and pathophysiologically relevant concentrations on the protein expression of TAS2R4, TAS2R5, TAS2R14, TAS2R20, TAS2R31, and TAS2R38 in subsets of monocytes and lymphocytes from the peripheral blood of healthy donors in vitro.
Materials and methods.
The study was performed on peripheral blood mononuclear cells from 10 healthy volunteers. The cells were incubated for 24 hours with recombinant IL-4 at concentrations of 0.1, 1, and 10 ng/ml. TAS2R expression was assessed by flow cytometry on a FACSCanto II with analysis of the proportion of TAS2R-positive cells and normalized median fluorescence intensity (nMFI). Page's test and Wilcoxon's test for related samples were used for statistical processing.
Results.
Under control conditions, all six studied receptors were detected in both monocytes and lymphocytes; however, their basal expression was significantly higher in monocytes. IL-4 exerted a pronounced dose-dependent inhibitory effect on TAS2R expression predominantly in monocytes. A monotonic downward trend was found for TAS2R4, TAS2R5, TAS2R14, and TAS2R38, while no significant changes were observed for TAS2R31. The most pronounced decrease in nMFI in monocytes was observed for TAS2R38, TAS2R14, and TAS2R5. TAS2R20 exhibited a biphasic response: an increase in the proportion of monocytes expressing TAS2R20 at the minimum dose of IL-4 was combined with a decrease in nMFI at 10 ng/ml. In lymphocytes, the effect of IL-4 was much less pronounced. Despite the presence of individual statistical trends, no biologically significant changes in TAS2R expressionwere detected.
Conclusion.
In a pilot in vitro experiment, IL-4 was associated with a monotonic decrease in TAS2R expression in peripheral blood monocytes, with relative stability of TAS2R31 and minimal effect in lymphocytes. These data expand our understanding of the subpopulation- and receptor-specific influence of the Th2 cytokine environment on TAS2R-dependent immunoregulation and suggest that IL-4 may be a potential factor in reducing the chemosensory and antimicrobial readiness of myeloid cells in asthma.