Oxidative stress as activators of sensory nerves for cough

Taylor‐Clark, Thomas E.

doi:10.1016/j.pupt.2015.06.003

Cited by 12 publications

(5 citation statements)

References 69 publications

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“… 43 TRPA1 can be activated by electrophiles through covalent modification of cysteine residues on the cytoplasmic N-terminus of the channel, 44 , 45 and this explains its sensitivity to reactive species that have an innate oxidative potential or the ability to generate intracellular oxidative stress. 44 , 46 In the present study we confirm that H 2 O 2 was also able to depolarize the vagus nerve in a TRPA1-dependent manner 30 , 47 and that responses to H 2 O 2 and DEP-OE were inhibited by the general antioxidant NAC. This is in general agreement with previous studies in which the effects of DEPs have been inhibited by application of NAC.…”

Section: Discussionsupporting

confidence: 84%

“… 29 Oxidative stress and the production of electrophiles have been shown to activate TRPA1 through covalent modification of cysteine residues. 30 , 31 , 32 The oxidant H 2 O 2 depolarized isolated guinea pig vagus nerve in a concentration-dependent manner (see Fig E5 , A , in this article's Online Repository at www.jacionline.org ). Janssen 130 (10 μmol/L) but not vehicle (0.1% DMSO) or TRPV1 antagonism significantly inhibited H 2 O 2 -induced depolarization in the guinea pig vagus nerve (see Fig E5 , B ).…”

Section: Resultsmentioning

confidence: 99%

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Mechanistic link between diesel exhaust particles and respiratory reflexes

Robinson

Birrell

Adcock

et al. 2018

Journal of Allergy and Clinical Immunology

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BackgroundDiesel exhaust particles (DEPs) are a major component of particulate matter in Europe's largest cities, and epidemiologic evidence links exposure with respiratory symptoms and asthma exacerbations. Respiratory reflexes are responsible for symptoms and are regulated by vagal afferent nerves, which innervate the airway. It is not known how DEP exposure activates airway afferents to elicit symptoms, such as cough and bronchospasm.ObjectiveWe sought to identify the mechanisms involved in activation of airway sensory afferents by DEPs.MethodsIn this study we use in vitro and in vivo electrophysiologic techniques, including a unique model that assesses depolarization (a marker of sensory nerve activation) of human vagus.ResultsWe demonstrate a direct interaction between DEP and airway C-fiber afferents. In anesthetized guinea pigs intratracheal administration of DEPs activated airway C-fibers. The organic extract (DEP-OE) and not the cleaned particles evoked depolarization of guinea pig and human vagus, and this was inhibited by a transient receptor potential ankyrin-1 antagonist and the antioxidant N-acetyl cysteine. Polycyclic aromatic hydrocarbons, major constituents of DEPs, were implicated in this process through activation of the aryl hydrocarbon receptor and subsequent mitochondrial reactive oxygen species production, which is known to activate transient receptor potential ankyrin-1 on nociceptive C-fibers.ConclusionsThis study provides the first mechanistic insights into how exposure to urban air pollution leads to activation of guinea pig and human sensory nerves, which are responsible for respiratory symptoms. Mechanistic information will enable the development of appropriate therapeutic interventions and mitigation strategies for those susceptible subjects who are most at risk.

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Section: Discussionsupporting

confidence: 84%

Section: Resultsmentioning

confidence: 99%

Mechanistic link between diesel exhaust particles and respiratory reflexes

Robinson

Birrell

Adcock

et al. 2018

Journal of Allergy and Clinical Immunology

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“…The inflammation includes neurogenic and contribution of various cells, such as eosinophils, lymphocytes, neutrophils, and mast cells 18 – 20 . Furthermore, Clark et al 12 recently revealed that mitochondrial reactive oxygen species activate airway sensory nerves, via TRP channels, and protein kinase C, and finally evoke cough reflexes. Citrate 21 , 22 exhibits anti-inflammatory and antioxidative properties as discussed below; thus, suggesting that decreased citric acid may fail to protect from airway inflammation and oxidative stress is plausible, which in turn leads to prolonged cough (Figure S2a).…”

Section: Discussionmentioning

confidence: 99%

“…Other potential mechanisms that underlie cough hypersensitivity syndrome include ion channels on C-fibers or airway sensory nerves, such as transient receptor potential (TRP) V1, V4, and A1 7 and prostaglandin E2 8 . Furthermore, the airway sensory nerves can be activated with airway inflammation 9 – 11 and oxidative stress 12 . However, the mechanisms that underlie prolonged or chronic cough remain largely unclear.…”

Section: Introductionmentioning

confidence: 99%

Association of lower plasma citric acid with prolonged cough: the Nagahama study

Terada,

Matsumoto,

Nishi

et al. 2023

Sci Rep

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Little is known about the association of prolonged cough, a common and troublesome symptom, with metabolic pathways. We aimed to clarify this association using data from the Nagahama cohort, a prospective study of participants from the general population. Self-report questionnaires on prolonged cough were collected at baseline and 5-year follow-up assessments. Blood tests at follow-up were used for gas chromatography-mass spectrometry-based metabolomics. The association between metabolites and prolonged cough was examined using the partial least squares discriminant analysis and multiple regression analysis. Among the 7432 participants, 632 had newly developed prolonged cough at follow-up, which was defined as “new-onset prolonged cough”. Low plasma citric acid was significantly associated with new-onset prolonged cough, even after the adjustment of confounding factors including the presence of asthma, upper airway cough syndrome (UACS), and gastroesophageal reflux disease (GERD). A similar association was observed for isocitric acid, 3-hydroxybutyric acid, and 3-hydroxyisobutyric acid. The analysis of these four metabolites revealed that citric acid had the strongest association with new-onset prolonged cough. This significant association remained even when the analysis was confined to participants with UACS or GERD at baseline or follow-up, and these associations were also observed in participants (n = 976) who had prolonged cough at follow-up regardless of baseline status. In conclusion, low blood citric acid may be associated with prolonged cough.

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“…It has been previously reported that increased airway oxidative stress is associated with chronic cough [ 24 ]. Recent work has indicated that oxidative stress, in particular downstream of mitochondrial dysfunction, activates airway nociceptive sensory nerves that may contribute to an excessive cough reflex [ 25 ]. One of the mechanisms underlying oxidative stress is through the increased expression of transforming growth factor β (TGFβ) levels in BALF and in the bronchial mucosa and in particular ASMCs and the airway epithelium of patients with chronic cough [ 26 ].…”

Section: Discussionmentioning

confidence: 99%

Impaired innate immune gene profiling in airway smooth muscle cells from chronic cough patients

et al. 2017

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Chronic cough is associated with airway inflammation and remodelling. Abnormal airway smooth muscle cell (ASMC) function may underlie mechanisms of chronic cough. Our objective was to examine the transcriptome and focused secretome of ASMCs from chronic cough patients and healthy non-cough volunteers. ASMC gene expression profiling was performed at baseline and/or after stimulation with polyinosinic:polycytidylic acid (poly(I:C)) to mimic viral infection. Supernatants were collected for multiplex analysis. Our results showed no significant differentially expressed genes (DEGs, false discovery rate (FDR) <0.05) between chronic cough and healthy non-cough ASMCs at baseline. Poly(I:C) stimulation resulted in 212 DEGs (>1.5 fold-change, FDR <0.05) in ASMCs from chronic cough patients compared with 1674 DEGs in healthy non-cough volunteers. The top up-regulated genes included chemokine (C–X–C motif) ligand (CXCL) 11 (CXCL11), CXCL10, chemokine (C–C motif) ligand (CCL) 5 (CCL5) and interferon-induced protein 44 like (IFI44L) corresponding with inflammation and innate immune response pathways. ASMCs from cough subjects had enhanced activation of viral response pathways in response to poly(I:C) compared with healthy non-cough subjects, reduced activation of pathways involved in chronic inflammation and equivalent activation of neuroregulatory genes. The poly(I:C)-induced release of inflammatory mediators, including CXCL8, interleukin (IL)-6 and CXCL1, from ASMCs from cough patients was significantly impaired compared with healthy non-cough subjects. Addition of fluticasone propionate (FP) to poly(I:C)-treated ASMCs resulted in greater gene expression changes in healthy non-cough ASMCs. FP had a differential effect on poly(I:C)-induced mediator release between chronic cough and healthy non-cough volunteers. In conclusion, altered innate immune and inflammatory gene profiles within ASMCs, rather than infiltrating cells or nerves, may drive the cough response following respiratory viral infection.

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Oxidative stress as activators of sensory nerves for cough

Cited by 12 publications

References 69 publications

Mechanistic link between diesel exhaust particles and respiratory reflexes

Mechanistic link between diesel exhaust particles and respiratory reflexes

Association of lower plasma citric acid with prolonged cough: the Nagahama study

Impaired innate immune gene profiling in airway smooth muscle cells from chronic cough patients

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