Modulating effect of TRPA1 and TRPM8 channels on cytokine production by pro- and anti-inflammatory macrophages

Introduction. Transient receptor potential (TRP) channels expressed on many cells, including macro­phages, are an attractive target for pharmacological modulation for the treatment of various diseases. At the same time, currently available data on the functional role of TRP on macrophages are scarce.Aim. To establish the effect of TRPA1 and TRPM8 channels on the production of cytokines by macrophages during pro-inflammatory (M1) and anti-inflammatory (M2) polarization.Materials and methods. Macrophages were obtained from monocytes of 8 healthy donors by differ­entiation in the presence of GM-CSF or M-CSF. Cell polarization was achieved by adding to the culture medium 100 ng/ml LPS + IFN-y 20 ng/ml (M1) or IL-4 20 ng/ml (M2) for 24 h. In order to modulate TRP activity, cinnamaldehyde 100 цМ (TRPA1 agonist), HC-030031 100 цМ (TRPA1 blocker), WS-12 10 цМ (TRPM8 agonist), or RQ-00434739 1 цМ (TRPM8 blocker) were used.Results. It was found that during M1 polarization TRPA1 channels inhibited the pro­duction of CXCL10, and TRPM8 increased the level of IL-8. Under polarization to the М2 phenotype, TRPA1 suppressed the production of pro-inflammatory cytokines IL-ie, TNF-a, IL-6, IL-12p70 and IFN-y, and TRPM8 did not significantly affect the levels of the analyzed mediators.Conclusion. The obtained results indicate that in terms of cytokine production by macrophages, TRPA1 has a predominantly anti-inflammatory effect, while TRPM8 shows a limited influence, which come to the regulation of IL-8 synthesis.