title: Activation of transient receptor potential ankyrin-1 (TRPA1) in lung cells by wood smoke particulate material.
abstract: Cigarette smoke, diesel exhaust, and other combustion-derived particles activate the calcium channel transient receptor potential ankyrin-1 (TRPA1), causing irritation and inflammation in the respiratory tract. It was hypothesized that wood smoke particulate and select chemical constituents thereof would also activate TRPA1 in lung cells, potentially explaining the adverse effects of wood and other forms of biomass smoke on the respiratory system. TRPA1 activation was assessed using calcium imaging assays in TRPA1-overexpressing HEK-293 cells, mouse primary trigeminal neurons, and human adenocarcinoma (A549) lung cells. Particles from pine and mesquite smoke were less potent agonists of TRPA1 than an equivalent mass concentration of an ethanol extract of diesel exhaust particles; pine particles were comparable in potency to cigarette smoke condensate, and mesquite particles were the least potent. The fine particulate (PM < 2.5 μm) of wood smoke were the most potent TRPA1 agonists and several chemical constituents of wood smoke particulate, 3,5-ditert-butylphenol, coniferaldehyde, formaldehyde, perinaphthenone, agathic acid, and isocupressic acid, were TRPA1 agonists. Pine particulate activated TRPA1 in mouse trigeminal neurons and A549 cells in a concentration-dependent manner, which was inhibited by the TRPA1 antagonist HC-030031. TRPA1 activation by wood smoke particles occurred through the electrophile/oxidant-sensing domain (i.e., C621/C641/C665/K710), based on the inhibition of cellular responses when the particles were pretreated with glutathione; a role for the menthol-binding site of TRPA1 (S873/T874) was demonstrated for 3,5-ditert-butylphenol. This study demonstrated that TRPA1 is a molecular sensor for wood smoke particulate and several chemical constituents thereof, in sensory neurons and A549 cells, suggesting that TRPA1 may mediate some of the adverse effects of wood smoke in humans.
authors.affiliation: Department of Pharmacology and Toxicology, University of Utah , 30 S. 2000 E., Room 201 Skaggs Hall, Salt Lake City, Utah 84112, United States.
authors.forename: Darien
authors.initials: D
authors.lastname: Shapiro
authors.forename: Cassandra E
authors.initials: CE
authors.lastname: Deering-Rice
authors.forename: Erin G
authors.initials: EG
authors.lastname: Romero
authors.forename: Ronald W
authors.initials: RW
authors.lastname: Hughen
authors.forename: Alan R
authors.initials: AR
authors.lastname: Light
authors.forename: John M
authors.initials: JM
authors.lastname: Veranth
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Reilly
mesh_terms: D000083:Acetanilides / Q000494:pharmacology; D000447:Aldehydes / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D015220:Calcium Channels / Q000235:genetics / Q000378:metabolism; D002264:Carboxylic Acids / Q000737:chemistry / Q000494:pharmacology; D045744:Cell Line, Tumor; D003998:Dicarboxylic Acids / Q000737:chemistry / Q000494:pharmacology; D004224:Diterpenes / Q000737:chemistry / Q000494:pharmacology; D057809:HEK293 Cells; D006801:Humans; D008168:Lung / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D008954:Models, Biological; D009419:Nerve Tissue Proteins / Q000819:agonists* / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D052638:Particulate Matter / Q000737:chemistry / Q000494:pharmacology*; D043803:Phenalenes / Q000737:chemistry / Q000494:pharmacology; D028223:Pinus / Q000737:chemistry; D029862:Prosopis / Q000737:chemistry; D011687:Purines / Q000494:pharmacology; D012906:Smoke / Q000009:adverse effects*; D013499:Surface Properties; D000074025:TRPA1 Cation Channel; D013764:Tetrahydronaphthalenes / Q000737:chemistry / Q000494:pharmacology; D050051:Transient Receptor Potential Channels / Q000819:agonists* / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D014276:Trigeminal Nerve / Q000166:cytology; D014934:Wood / Q000737:chemistry*
chemical_list: C552888:2-(1,3-dimethyl-2,6-dioxo-1,2,3,6-tetrahydro-7H-purin-7-yl)-N-(4-isopropylphenyl)acetamide; D000083:Acetanilides; D000447:Aldehydes; D015220:Calcium Channels; D002264:Carboxylic Acids; D003998:Dicarboxylic Acids; D004224:Diterpenes; D009419:Nerve Tissue Proteins; D052638:Particulate Matter; D043803:Phenalenes; D011687:Purines; D012906:Smoke; D000074025:TRPA1 Cation Channel; C473350:TRPA1 protein, human; D013764:Tetrahydronaphthalenes; D050051:Transient Receptor Potential Channels; C475685:Trpa1 protein, mouse; C110793:isocupressic acid; C038036:phenalen-1-one; C110795:agathic acid
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