Transient Receptor Potential Vanilloid-1 (TRPV1) Is a Mediator of Lung Toxicity for Coal Fly Ash Particulate Material

Deering-Rice, Cassandra E.; Johansen, Mark E.; Roberts, Jessica K.; Thomas, Karen C.; Romero, Erin G.; Lee, Jeeyeon; Yost, Garold S.; Veranth, John M.; Reilly, Christopher A.

doi:10.1124/mol.111.076067

Cited by 58 publications

(81 citation statements)

References 51 publications

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“…Both of these sites have been previously evaluated for their role in modulating TRPA1 activation by DEP and biomass smoke particles, with electrophilic compounds associated with these types of PM being principally responsible for TRPA1 activation (2, 3). Data presented in Figures 2 through 7, which are summarized in Table 3, expand upon results initially presented by Deering-Rice and colleagues (2) by conclusively showing that DEP and CFA activate TRPA1 via a third mechanism involving specific interactions with insoluble components of the PM, similar to that reported for TRPV1 (1). N-linked glycosylation plays a major role in the subcellular localization and function of TRP channels (33).…”

Section: Discussionsupporting

confidence: 67%

“…TRPA1 is activated by soluble chemicals associated with DEP, solvent-"stripped" insoluble soot material from DEP (2), and wood smoke PM (3). Previous studies investigating the mechanical activation of TRPV1 suggest that PM may interact with proteoglycans on the surface of the protein (1). However, this mechanism of TRPA1 activation by insoluble PM has not been explored.…”

mentioning

confidence: 96%

“…It has been shown that components of urban PM, such as diesel exhaust PM (DEP), activate airway neurons that express transient receptor potential (TRP) ankyrin-1 (TRPA1) and TRP vanilloid-1 (TRPV1) (1)(2)(3)(4)(5)(6)(7)(8). TRPA1 and TRPV1 are members of the TRP family of ion channels.…”

mentioning

confidence: 99%

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Activation of Transient Receptor Potential Ankyrin-1 by Insoluble Particulate Material and Association with Asthma

Deering-Rice

Shapiro

Romero

et al. 2015

Am J Respir Cell Mol Biol

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Inhaled irritants activate transient receptor potential ankyrin-1 (TRPA1), resulting in cough, bronchoconstriction, and inflammation/edema. TRPA1 is also implicated in the pathogenesis of asthma. Our hypothesis was that particulate materials activate TRPA1 via a mechanism distinct from chemical agonists and that, in a cohort of children with asthma living in a location prone to high levels of air pollution, expression of uniquely sensitive forms of TRPA1 may correlate with reduced asthma control. Variant forms of TRPA1 were constructed by mutating residues in known functional elements and corresponding to single-nucleotide polymorphisms in functional domains. TRPA1 activity was studied in transfected HEK-293 cells using allyl-isothiocynate, a model soluble electrophilic agonist; 3,5-ditert butylphenol, a soluble nonelectrophilic agonist and a component of diesel exhaust particles; and insoluble coal fly ash (CFA) particles. The N-terminal variants R3C and R58T exhibited greater, but not additive, activity with all three agonists. The ankyrin repeat domain-4 single nucleotide polymorphisms E179K and K186N exhibited decreased response to CFA. The predicted N-linked glycosylation site residues N747A and N753A exhibited decreased responses to CFA, which were not attributable to differences in cellular localization. The pore-loop residue R919Q was comparable to wild-type, whereas N954T was inactive to soluble agonists but not CFA. These data identify roles for ankyrin domain-4, cell surface N-linked glycans, and selected pore-loop domain residues in the activation of TRPA1 by insoluble particles. Furthermore, the R3C and R58T polymorphisms correlated with reduced asthma control for some children, which suggest that TRPA1 activity may modulate asthma, particularly among individuals living in locations prone to high levels of air pollution.

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Section: Discussionsupporting

confidence: 67%

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confidence: 96%

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Activation of Transient Receptor Potential Ankyrin-1 by Insoluble Particulate Material and Association with Asthma

Deering-Rice

Shapiro

Romero

et al. 2015

Am J Respir Cell Mol Biol

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“…In this regard, nerve fibers in the lung have been shown to be activated in response to acrolein (a component of cigarette smoke) or capsaicin through the activation of transient receptor potential (TRP) channels, a superfamily of cation channels that are present on the plasma membrane of many cells including nerve fibers (57,58). Over 26 TRP channels have been described, and at least 2 of these channels, TRPA1 and TRPV1, have been reported to be activated by PM and play a role in PM-induced lung inflammation; however, it is not known whether they play a role in the PM-induced activation of the sympathetic nervous system (59,60).…”

Section: Discussionmentioning

confidence: 99%

β2-Adrenergic agonists augment air pollution–induced IL-6 release and thrombosis

Chiarella¹,

Soberanes²,

Urich³

et al. 2014

J. Clin. Invest.

109

101

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Acute exposure to particulate matter (PM) air pollution causes thrombotic cardiovascular events, leading to increased mortality rates; however, the link between PM and cardiovascular dysfunction is not completely understood. We have previously shown that the release of IL-6 from alveolar macrophages is required for a prothrombotic state and acceleration of thrombosis following exposure to PM. Here, we determined that PM exposure results in the systemic release of catecholamines, which engage the β 2 -adrenergic receptor (β 2 AR) on murine alveolar macrophages and augment the release of IL-6. In mice, β 2 AR signaling promoted the development of a prothrombotic state that was sufficient to accelerate arterial thrombosis. In primary human alveolar macrophages, administration of a β 2 AR agonist augmented IL-6 release, while the addition of a beta blocker inhibited PM-induced IL-6 release. Genetic loss or pharmacologic inhibition of the β 2 AR on murine alveolar macrophages attenuated PM-induced IL-6 release and prothrombotic state. Furthermore, exogenous β 2 AR agonist therapy further augmented these responses in alveolar macrophages through generation of mitochondrial ROS and subsequent increase of adenylyl cyclase activity. Together, these results link the activation of the sympathetic nervous system by β 2 AR signaling with metabolism, lung inflammation, and an enhanced susceptibility to thrombotic cardiovascular events.

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“…1 (TRPA1) and TRP vanilloid 1 (TRPV1), in the cardiovascular effects of PM, suggesting a role for cardiovascular reflexes initiated from the airways (2,15,16,22).…”

mentioning

confidence: 99%

Characterization of cardiovascular reflexes evoked by airway stimulation with allylisothiocyanate, capsaicin, and ATP in Sprague-Dawley rats

Hooper

Hadley

Morris

et al. 2016

Journal of Applied Physiology

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Acute inhalation of airborne pollutants alters cardiovascular function and evidence suggests that pollutant-induced activation of airway sensory nerves via the gating of ion channels is critical to these systemic responses. Here, we have investigated the effect of capsaicin [transient receptor potential (TRP) vanilloid 1 (TRPV1) agonist], AITC [TRP ankyrin 1 (TRPA1) agonist], and ATP (P2X2/3 agonist) on bronchopulmonary sensory activity and cardiovascular responses of conscious Sprague-Dawley (SD) rats. Single fiber recordings show that allyl isothiocyanate (AITC) and capsaicin selectively activate C fibers, whereas subpopulations of both A and C fibers are activated by stimulation of P2X2/3 receptors. Inhalation of the agonists by conscious rats caused significant bradycardia, atrioventricular (AV) block, and prolonged PR intervals, although ATP-induced responses were lesser than those evoked by AITC or capsaicin. Responses to AITC were inhibited by the TRP channel blocker ruthenium red and the muscarinic antagonist atropine. AITC inhalation also caused a biphasic blood pressure response: a brief hypertensive phase followed by a hypotensive phase. Atropine accentuated the hypertensive phase, while preventing the hypotension. AITC-evoked bradycardia was not abolished by terazosin, the α1-adrenoceptor inhibitor, which prevented the hypertensive response. Anesthetics had profound effects on AITC-evoked bradycardia and AV block, which was abolished by urethane, ketamine, and isoflurane. Nevertheless, AITC inhalation caused bradycardia and AV block in paralyzed and ventilated rats following precollicular decerebration. In conclusion, we provide evidence that activation of ion channels expressed on nociceptive airway sensory nerves causes significant cardiovascular effects in conscious SD rats via reflex modulation of the autonomic nervous system.

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Transient Receptor Potential Vanilloid-1 (TRPV1) Is a Mediator of Lung Toxicity for Coal Fly Ash Particulate Material

Cited by 58 publications

References 51 publications

Activation of Transient Receptor Potential Ankyrin-1 by Insoluble Particulate Material and Association with Asthma

Activation of Transient Receptor Potential Ankyrin-1 by Insoluble Particulate Material and Association with Asthma

β2-Adrenergic agonists augment air pollution–induced IL-6 release and thrombosis

Characterization of cardiovascular reflexes evoked by airway stimulation with allylisothiocyanate, capsaicin, and ATP in Sprague-Dawley rats

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