Peculiarities of TRPV1, TRPV4, TRPM8 and TRPA1 expression in monocyte-derived macrophages from COPD patients

Introduction. Macrophages are key cells of the innate immune system possessing high functional plasticity. Previously, some transient receptor potential (TRP) channels were identified on macrophages, including those that are receptors for cigarette smoke and particulate matter, which may play an important role in the pathogenesis of chronic obstructive pulmonary disease (COPD).
Aim. The aim of this study was to investigate the expression of TRPV1, TRPV4, TRPM8, and TRPA1 in monocyte-derived macrophages from COPD patients under stimulation with lipopolysaccharides (LPS) and interferon-gamma (IFNγ) or interleukin 4 (IL-4).
Materials and methods. Macrophages were differentiated in vitro in the presence of granulocyte-macrophage colony-stimulating factor from monocytes obtained from COPD patients. The concentration of cytokines was determined in the supernatant of the culture medium after stimulation by multiplex analysis. The expression of TRP genes in macrophages was evaluated at mRNA level by quantitative PCR with reverse transcription.
Results. The effect of LPS/IFNγ was accompanied by the production of both proinflammatory (IL-1β, IL6, IL-12p70, IP-10, TNFα) and some anti-inflammatory cytokines (IL-4, IL-10 and TGFβ1). IL-4 significantly increased the concentration of IL-17A. Stimulation of macrophages with LPS/IFNγ increased the expression of TRPA1 by 5.6 times (p = 0.01) but caused down-regulation of TRPV1 and TRPV4 by 8.5 (p = 0.007) and 3.2 (p = 0.03) times, respectively. IL4 did not exert any effect on the TRP gene expression.
Conclusions. The results obtained may indicate dysregulation of the immune response in patients with COPD, primarily due to a decrease of anti-inflammatory potential of macrophages. The observed LPS-induced changes in the expression of TRP channels apparently have a compensatory nature and are aimed at the limitation of the cellular inflammatory response.

monocytes, macrophages, TRP channels, inflammation, cigarette smoke, COPD

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