Role of the ion channel, transient receptor potential cation channel subfamily V member 1 (TRPV1), in allergic asthma

Abstract

BackgroundAsthma prevalence has increased world-wide especially in children; thus there is a need to develop new therapies that are safe and effective especially for patients with severe/refractory asthma. CD4+ T cells are thought to play a central role in disease pathogenesis and associated symptoms. Recently, TRPV1 has been demonstrated to regulate the activation and inflammatory properties of CD4+ cells. The aim of these experiments was to demonstrate the importance of CD4+ T cells and the role of TRPV1 in an asthma model using a clinically ready TRPV1 inhibitor (XEN-D0501) and genetically modified (GM) animals.MethodsMice (wild type, CD4 −/− or TRPV1 −/−) and rats were sensitised with antigen (HDM or OVA) and subsequently topically challenged with the same antigen. Key features associated with an allergic asthma type phenotype were measured: lung function (airway hyperreactivity [AHR] and late asthmatic response [LAR]), allergic status (IgE levels) and airway inflammation.ResultsCD4+ T cells play a central role in both disease model systems with all the asthma-like features attenuated. Targeting TRPV1 using either GM mice or a pharmacological inhibitor tended to decrease IgE levels, airway inflammation and lung function changes.ConclusionOur data suggests the involvement of TRPV1 in allergic asthma and thus we feel this target merits further investigation.

The emerging role of transient receptor potential channels in chronic lung disease

“…In addition, an impact was observed on the LAR. Although many of the effects seen in this study did not reach statistical significance there was a consistent suppression across the functional end-points measured, suggesting a discrete role for TRPV1 in driving CD4 + -dependent allergic asthma models [122].…”

“…Consistent with these findings, another study suggests that TRPV1, and not TRPA1, plays a discrete role in modulating aspects of the asthma phenotype in a house dust mite-driven murine model reducing plasma IgE levels, airway cellular inflammation and airway hyperresponsiveness. In this study confirmation was obtained in an alternative model system utilising a second species, the Brown Norway rat, an alternative antigen; ovalbumin and a small-molecule TRPV1 inhibitor, XEN-D0501 [122]. Interestingly, the effect of XEN-D0501 on cellular inflammation, when dosed around the challenge, was similar to that observed in TRPV1 −/− mice, but the levels of IgE remained unchanged, consistent with an effect in the challenge phase of the model [122].…”

“…In this study confirmation was obtained in an alternative model system utilising a second species, the Brown Norway rat, an alternative antigen; ovalbumin and a small-molecule TRPV1 inhibitor, XEN-D0501 [122]. Interestingly, the effect of XEN-D0501 on cellular inflammation, when dosed around the challenge, was similar to that observed in TRPV1 −/− mice, but the levels of IgE remained unchanged, consistent with an effect in the challenge phase of the model [122]. In addition, an impact was observed on the LAR.…”

“…A role for TRPA1 has been demonstrated in murine models of allergic asthma utilising small molecule antagonists and TRPA1 −/− mice with an inhibitory effect on inflammatory mediator and mucus production, leukocyte infiltration and airway hyperresponsiveness (AHR) to acetylcholine [118]. In addition, TRPA1 −/− mice displayed deficiencies in allergen-induced neuropeptide release in the airways, which the authors suggested provided a potential explanation for the impaired inflammatory response, although the rationale for this is not completely clear and this finding was not reproduced in other studies [122]. Interestingly, a role for TRPA1 has also been proposed in nonallergic inflammation in a study set up in a murine model which aimed to recapitulate incidents of AHR experienced by swimmers due to increased exposure to hypochlorite.…”

Aspectos fisiopatológicos do reflexo da tosse: uma revisão de literatura

“…Além das células neuronais, o TRPV1 é um canal catiónico não seletivo presente no músculo liso e epitélio do trato respiratório e na membrana plasmática dos neurônios sensoriais que inervam as vias aéreas superiores e inferiores 24 . O TRPV1 pode ser ativado por uma gama diversificada de ligantes químicos endógenos e exógenos, compostos vanilóides como a capsaicina, metabolitos de ácido araquidônico endógeno, pH baixo e temperaturas acima de 43°C [25][26][27][28][29][30][31][32][33] . Nesse sentido, estudos constataram que os receptores TRPV1 são superexpressados em pacientes com tosse crônica 34 .…”