Effect of budesonide, formoterol and tiotropium on the expression of TRPV1 and TRPV4 cation channels in peripheral blood mononuclear cells in vitro

Introduction. Experimental evidence has demonstrated that the cation channels TRPV1 and TRPV4 are involved in the development of various pathological processes characteristic of asthma and chronic obstructive pulmonary disease (COPD) and, therefore, may be considered potential therapeutic targets for these diseases.

Aim. To analyze the effects of the maintenance therapy drugs used for asthma and COPD – budesonide, formoterol, and tiotropium – on the expression of TRPV1 and TRPV4 proteins in peripheral blood mononuclear cells in vitro.

Materials and methods. Mononuclear cells for the experiment were isolated from the blood of 9 apparently healthy volunteers. The cells were incubated under control conditions or in medium containing budesonide, formoterol fumarate, or tiotropium bromide at concentrations of 1, 10, or 100 nM for 24 hours. After incubation, the cells were washed, and total TRPV1 and TRPV4 expression was analyzed by indirect flow cytometry. Expression values were presented as normalized median fluorescence intensity (nMFI).

Results. Budesonide, formoterol, and tiotropium significantly reduced TRPV1 expression in lymphocytes and monocytes at all analyzed concentrations. For example, baseline TRPV1 expression in lymphocytes was 5.3 (4.9; 5.6), whereas exposure to 10 nM budesonide reduced it to 3.0 (2.6; 3.9) (p = 0.008), formoterol – to 2.8 (2.7; 3.6) (p = 0.01), and tiotropium – to 2.8 (2.4; 3.0) (p = 0.008). The corresponding values for monocytes were 4.9 (4.6; 6.8) (p = 0.02), 4.4 (4.1; 6.4) (p = 0.02), and 4.3 (3.6; 4.7) (p = 0.01), respectively, compared with baseline expression of 10.2 (8.0; 10.3). At the same time, the inhibitory effect of the drugs on TRPV4 expression was observed predominantly in lymphocytes: 10 nM budesonide, formoterol, and tiotropium reduced channel expression from 1.4 (1.3; 1.6) to 1.1 (1.0; 1.5) (p = 0.04), 1.0 (0.9; 1.4) (p = 0.04), and 1.0 (0.9; 1.3) (p = 0.03), respectively.

Conclusion. It was established for the first time that budesonide, formoterol, and tiotropium can reduce the expression of TRPV1 and TRPV4 cation channels in peripheral blood mononuclear cells in vitro. The obtained results expand current understanding of the pharmacological effects of asthma and COPD maintenance therapy and suggest the existence of an additional common component of their pharmacological action associated with the regulation of TRPV1/TRPV4 channels.

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