Dysfunction of transient receptor potential ion channels as an important pathophysiological mechanism in asthma

Abstract

Asthma is a chronic heterogeneous disease characterized by chronic inflammation and bronchial hyperreactivity. Neurogenic inflammation is one of the important causes of hyperreactivity. Dysfunction of transient receptor potential (TRP) ion channels underlies the development of neurogenic inflammation, bronchial hyperreactivity and respiratory symptoms of asthma such as bronchospasm and cough. TRP channels are expressed in the respiratory tract. Their activation is mediated by endogenous and exogenous factors involved in the pathogenesis of asthma. The study of functioning and regulation of TRP channels is relevant, as they could be important therapeutic targets for asthma. The aim of the review is to summarize modern ideas about the mechanisms of functioning and regulation of members of the TRP channel superfamily, the role of which in lung pathology and physiology are the best studied.

A review of the pathophysiology and the role of ion channels on bronchial asthma

“…In recent years, there has been evidence highlighting the significant role of TRP channels in respiratory diseases, including asthma ( Kytikova et al, 2020 ). The activation of these channels contributes to inflammatory processes and structural alterations in the respiratory tract, leading to bronchoconstriction ( Taylor-Clark, 2016 ).…”

“…This response was also observed through the positive modulation of TRPV1 channels ( Moran et al, 2011 ; McMahon et al, 2015 ), taking into account that the neurogenic inflammation caused by the release of these neuropeptides contributed to the worsening of asthma. This condition also occurred due to the production of cytokines such as tumor necrosis factor-α, IL-1, IL-6 and IL-8 by human bronchial epithelial cells, considering that these factors can cause bronchoconstriction ( Lee and Yang, 2012 ; Song et al, 2017 ; Kytikova et al, 2020 ).…”

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“…As mentioned above, asthma therapy includes inhaled β2-AR agonists, inhaled and systemic GCs, LTSIs and LTRAs [15]. Resistance to GCs in patients with severe asthma remains a serious clinical problem [16][17][18]160]. GC resistance depends on the expression and affinity of GR, as well as many intracellular mediators controlling the signal transduction pathway [149,161].…”

“…At the same time, such therapy is not effective enough in 5-10% of cases [16]. Besides, extended GCS administration results in numerous side effects, which reduces the efficacy of treatment [17,18]. Hence, further studies of the regulatory mechanisms of inflammation and ways of its resolution in asthma are essential.…”

Medium and long chain free fatty acid receptors in the pathophysiology of respiratory diseases

“…Широкая распространенность и трудность контроля течения хронических воспалительных заболеваний дыхательных путей, включая бронхиальную астму (БА) и хроническую обструктивную болезнь легких (ХОБЛ), указывает на необходимость выявления новых терапевтических мишеней [1,2]. В последние годы наблюдается интерес к изучению не только нейроиммунных механизмов хронизации воспаления в бронхолегочной системе [3,4], но и метаболических изменений, обусловленных нарушениями состава жирных кислот (ЖК) мембран клеток и синтеза липидных медиаторов, участвующих в разрешении острого воспаления [5][6][7]. Дисбаланс иммунной и метаболической систем имеет тесную двустороннюю взаимосвязь [8].…”