No full-text available
To read the full-text of this research,
you can request a copy directly from the authors.
The activation of transient receptor potential melastatin 8 (TRPM8) receptors of bronchial epithelial cells induces airway inflammation in bronchial asthma
Abstract
Background: Cold air is a major environmental factor that exacerbates bronchial asthma. Transient receptor potential melastatin family member 8 (TRPM8) receptor is a cold- and menthol-sensing cation channel expressed in sensory neurons as well as bronchial epithelial cells.
Objectives: We sought to explore the role of TRPM8 receptor expressed in bronchial epithelial cells in airway inflammation.
Methods: Human airway epithelial cell line, BEAS-2B, was treated with menthol, TRPM8 antagonist (BCTC, N-(4-tert-butylphenyl)-4-(3-chloropyridin-2-yl) piperazine-1-carboxamide) and dexamethasone in dose- and time- dependent manner. The mRNA of TRPM8 and proinflammatory cytokines such as IL-4, 6, 8, 13, 25, 33 was determined by real-time quantitative PCR. The expression of TRPM8 in bronchial epithelial cells was determined by western blotting and immunofluorescence. ELISA of TRPM8 performed using the induced sputum of asthmatics and normal controls.
Results: TRPM8 protein expression was significantly increased in patients with asthma compared with healthy controls using ELISA of sputum supernatants. TRPM8 receptor was expressed primarily in bronchial epithelial cells at both mRNA and protein levels with statistical significances. Activating TRPM8 receptors by menthol was coupled with enhanced expression of the inflammatory cytokines of some IL and treatment with BCTC and dexamethasone attenuated the expression of the inflammatory cytokines.
Conclusions: Activation of TRPM8 receptor of bronchial epithelial cells induces airway inflammatory cytokines, suggesting the TRPM8 receptor may involve in cold induced asthma exacerbations.
... TRP channel activation in the nerve endings of the respiratory tract leads to the stimulation of protective reflexes, but under certain conditions, it can be the pathogenetic basis of asthma [12][13][14][15]. The role of TRP channels in asthma pathogenesis has been demonstrated [13,[16][17][18][19][20][21], which makes them promising targets for disease therapy [12,13]. ...
... It is known that thermosensory TRP channels are responsible for the reception of physicochemical environmental stimuli and the regulation of body temperature [5,8,9,[42][43][44]. The impairment of their functioning plays an important role in asthma pathogenesis [16][17][18][19][20][21]45], which makes these channels promising targets for disease treatment [12,46]. ...
... TRP channels are expressed primarily by neuronal cells. At the same time, the channels were also found on other cells, particularly in the respiratory tract (bronchial epithelium and endothelium, smooth muscle cells, non-myelinated nociceptive C-fibers of the lungs) [11,16,[18][19][20]43,50,[52][53][54][55][56][57][58][59] (Table 2). The operating principle of these receptors is the activation of cation influx in response to stimuli [47]. ...
Asthma is a widespread chronic disease of the bronchopulmonary system with a heterogeneous course due to the complex etiopathogenesis. Natural-climatic and anthropogenic factors play an important role in the development and progression of this pathology. The reception of physical and chemical environmental stimuli and the regulation of body temperature are mediated by thermosensory channels, members of a subfamily of transient receptor potential (TRP) ion channels. It has been found that genes encoding vanilloid, ankyrin, and melastatin TRP channels are involved in the development of some asthma phenotypes and in the formation of exacerbations of this pathology. The review summarizes modern views on the role of high and low temperatures in airway inflammation in asthma. The participation of thermosensory TRP channels (vanilloid, ankyrin, and melastatin TRP channels) in the reaction to high and low temperatures and air humidity as well as in the formation of bronchial hyperreactivity and respiratory symptoms accompanying asthma is described. The genetic aspects of the functioning of thermosensory TRP channels are discussed. It is shown that new methods of treatment of asthma exacerbations caused by the influence of temperature and humidity should be based on the regulation of channel activity.
... As with many TRP channels, TRPM8 does not have only antiinflammatory properties but pro-inflammatory properties as well. For example, asthmatic patients have an upregulation of TRPM8 expression in bronchial epithelial cells and sputum (110,188). Unlike the analgesic effects produced in colitis or nerve injury, TRPM8 function in the lungs triggers bronchial inflammation through prolonged cold air inhalation. These responses can be replicated in models of pulmonary cold exposure and menthol treatment, causing a significant increase in IL-6, IL-8, and interleukin 25/thymic stromal lymphopoietin receptor (TSLP) mRNA expression (110,111). ...
Transient receptor potential (TRP) channels are a superfamily of non-selective cation channels that act as polymodal sensors in many tissues throughout mammalian organisms. In the context of ion channels, they are unique for their broad diversity of activation mechanisms and their cation selectivity. TRP channels are involved in a diverse range of physiological processes including chemical sensing, nociception, and mediating cytokine release. They also play an important role in the regulation of inflammation through sensory function and the release of neuropeptides. In this review, we discuss the functional contribution of a subset of TRP channels (TRPV1, TRPV4, TRPM3, TRPM8, and TRPA1) that are involved in the body’s immune responses, particularly in relation to inflammation. We focus on these five TRP channels because, in addition to being expressed in many somatic cell types, these channels are also expressed on peripheral ganglia and nerves that innervate visceral organs and tissues throughout the body. Activation of these neural TRP channels enables crosstalk between neurons, immune cells, and epithelial cells to regulate a wide range of inflammatory actions. TRP channels act either through direct effects on cation levels or through indirect modulation of intracellular pathways to trigger pro- or anti-inflammatory mechanisms, depending on the inflammatory disease context. The expression of TRP channels on both neural and immune cells has made them an attractive drug target in diseases involving inflammation. Future work in this domain will likely yield important new pathways and therapies for the treatment of a broad range of disorders including colitis, dermatitis, sepsis, asthma, and pain.
The aim of the study was to analyze the peculiarities of TRPM8 receptor expression at protein level in induced sputum and nasal epithelium of asthma patients, and to evaluate their relationship to maintenance therapy and cold airway hyperresponsiveness. The study enrolled 43 patients, including those with persistent mild-to-moderate asthma and those with chronic non-obstructive bronchitis (control group). Analysis of TRPM8 expression was performed by indirect flow cytometry. In addition, patients underwent spirometry and a bronchoprovocation test with 3-minute cold air hyperventilation. As a result, we found that TRPM8 was expressed on macrophages of induced spleen and nasal epithelium. Its expression in patients with asthma who did not receive maintenance therapy was more pronounced as compared to the treated patients or the control group. Moreover, the relationship between increased expression of TRPM8 on macrophages and cold airway hyperresponsiveness was established. Further studies should reveal the possibility of TRPM8 usage as a prognostic biomarker of asthma at various stages of the disease development.
ResearchGate has not been able to resolve any references for this publication.