Peculiarities of TRP channels expression and cytokine profile of sputum in patients with chronic obstructive pulmonary disease and progressive bronchial obstruction

Abstract

Introduction. Chronic obstructive pulmonary disease (COPD) is a pathology accompanied by a pro­gressive and irreversible deterioration in airway patency. It is known that macrophages of the respiratory tract are actively involved in the reorganization of the extracellular matrix leading to the development of bronchial remodeling.Aim. To assess the relationship between the progression rate of bronchial obstruction in COPD, the expression of TRP channels on alveolar macrophages, and the levels of inflammatory markers in the respiratory tract.Materials and methods. The study enrolled 37 patients with COPD, including 23 people with a FEV1 deterioration >50 ml/year and 14 with FEV1 decline <50 ml/year. The expression of TRPV1, TRPV4, TRPA1, TRPM8 channels was determined on alveolar macrophages by flow cytometry. Analysis of cytokines was performed in sputum supernatant by multiplex assay on a flow cytometer.Re­sults. It was found that in patients with progressive bronchial obstruction TRPV4 expression was significantly increased: 14.2 (10.8; 23.4)% vs. 8.6 (3.6; 15.4)% (p=0.03). In addition, in the general group of patients a highly significant inverse correlation was found between TRPV4 expression and the dynamics of FEV1 (p=-0.52, p<0.001). Patients with a decrease in FEV1 >50 ml/year were characterized by significantly elevated levels of IL-2, IL-4, IL-17A, IL-10, IL-12p70, CXCL10 and MCP-1. Additionally, we found that concentrations of several cytokines were directly correlated with TRPV4 expres­sion on macrophages: IL-4 (p=0.51, p=0.001), CXCL10 (p=0.59, p<0.001), MCP-1 (p=0.56, p<0.001), TGF-ei (p=0.42, p=0.009), IFN-y (p=0.37, p=0.02).Conclusion. TRPV4 channels expressed on alveolar macrophages are involved in the inflammatory process and airway remodeling in COPD, which is manifested by their relationships with the level of certain cytokines production, as well as the rate of the progression of bronchial obstruction.