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Transient receptor potential ankyrin 1 channel localized to non-neuronal airway cells promotes non-neurogenic inflammation.
PLoS One. 2012; 7(8):e42454.Plos

Abstract

BACKGROUND

The transient receptor potential ankyrin 1 (TRPA1) channel, localized to airway sensory nerves, has been proposed to mediate airway inflammation evoked by allergen and cigarette smoke (CS) in rodents, via a neurogenic mechanism. However the limited clinical evidence for the role of neurogenic inflammation in asthma or chronic obstructive pulmonary disease raises an alternative possibility that airway inflammation is promoted by non-neuronal TRPA1.

METHODOLOGY/PRINCIPAL FINDINGS

By using Real-Time PCR and calcium imaging, we found that cultured human airway cells, including fibroblasts, epithelial and smooth muscle cells express functional TRPA1 channels. By using immunohistochemistry, TRPA1 staining was observed in airway epithelial and smooth muscle cells in sections taken from human airways and lung, and from airways and lung of wild-type, but not TRPA1-deficient mice. In cultured human airway epithelial and smooth muscle cells and fibroblasts, acrolein and CS extract evoked IL-8 release, a response selectively reduced by TRPA1 antagonists. Capsaicin, agonist of the transient receptor potential vanilloid 1 (TRPV1), a channel co-expressed with TRPA1 by airway sensory nerves, and acrolein or CS (TRPA1 agonists), or the neuropeptide substance P (SP), which is released from sensory nerve terminals by capsaicin, acrolein or CS), produced neurogenic inflammation in mouse airways. However, only acrolein and CS, but not capsaicin or SP, released the keratinocyte chemoattractant (CXCL-1/KC, IL-8 analogue) in bronchoalveolar lavage (BAL) fluid of wild-type mice. This effect of TRPA1 agonists was attenuated by TRPA1 antagonism or in TRPA1-deficient mice, but not by pharmacological ablation of sensory nerves.

CONCLUSIONS

Our results demonstrate that, although either TRPV1 or TRPA1 activation causes airway neurogenic inflammation, solely TRPA1 activation orchestrates an additional inflammatory response which is not neurogenic. This finding suggests that non-neuronal TRPA1 in the airways is functional and potentially capable of contributing to inflammatory airway diseases.

Authors+Show Affiliations

Department of Preclinical and Clinical Pharmacology, University of Florence, Florence, Italy.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

22905134

Citation

Nassini, Romina, et al. "Transient Receptor Potential Ankyrin 1 Channel Localized to Non-neuronal Airway Cells Promotes Non-neurogenic Inflammation." PloS One, vol. 7, no. 8, 2012, pp. e42454.
Nassini R, Pedretti P, Moretto N, et al. Transient receptor potential ankyrin 1 channel localized to non-neuronal airway cells promotes non-neurogenic inflammation. PLoS One. 2012;7(8):e42454.
Nassini, R., Pedretti, P., Moretto, N., Fusi, C., Carnini, C., Facchinetti, F., Viscomi, A. R., Pisano, A. R., Stokesberry, S., Brunmark, C., Svitacheva, N., McGarvey, L., Patacchini, R., Damholt, A. B., Geppetti, P., & Materazzi, S. (2012). Transient receptor potential ankyrin 1 channel localized to non-neuronal airway cells promotes non-neurogenic inflammation. PloS One, 7(8), e42454. https://doi.org/10.1371/journal.pone.0042454
Nassini R, et al. Transient Receptor Potential Ankyrin 1 Channel Localized to Non-neuronal Airway Cells Promotes Non-neurogenic Inflammation. PLoS One. 2012;7(8):e42454. PubMed PMID: 22905134.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Transient receptor potential ankyrin 1 channel localized to non-neuronal airway cells promotes non-neurogenic inflammation. AU - Nassini,Romina, AU - Pedretti,Pamela, AU - Moretto,Nadia, AU - Fusi,Camilla, AU - Carnini,Chiara, AU - Facchinetti,Fabrizio, AU - Viscomi,Arturo Roberto, AU - Pisano,Anna Rita, AU - Stokesberry,Susan, AU - Brunmark,Charlott, AU - Svitacheva,Naila, AU - McGarvey,Lorcan, AU - Patacchini,Riccardo, AU - Damholt,Anders B, AU - Geppetti,Pierangelo, AU - Materazzi,Serena, Y1 - 2012/08/14/ PY - 2012/04/13/received PY - 2012/07/06/accepted PY - 2012/8/21/entrez PY - 2012/8/21/pubmed PY - 2013/2/12/medline SP - e42454 EP - e42454 JF - PloS one JO - PLoS One VL - 7 IS - 8 N2 - BACKGROUND: The transient receptor potential ankyrin 1 (TRPA1) channel, localized to airway sensory nerves, has been proposed to mediate airway inflammation evoked by allergen and cigarette smoke (CS) in rodents, via a neurogenic mechanism. However the limited clinical evidence for the role of neurogenic inflammation in asthma or chronic obstructive pulmonary disease raises an alternative possibility that airway inflammation is promoted by non-neuronal TRPA1. METHODOLOGY/PRINCIPAL FINDINGS: By using Real-Time PCR and calcium imaging, we found that cultured human airway cells, including fibroblasts, epithelial and smooth muscle cells express functional TRPA1 channels. By using immunohistochemistry, TRPA1 staining was observed in airway epithelial and smooth muscle cells in sections taken from human airways and lung, and from airways and lung of wild-type, but not TRPA1-deficient mice. In cultured human airway epithelial and smooth muscle cells and fibroblasts, acrolein and CS extract evoked IL-8 release, a response selectively reduced by TRPA1 antagonists. Capsaicin, agonist of the transient receptor potential vanilloid 1 (TRPV1), a channel co-expressed with TRPA1 by airway sensory nerves, and acrolein or CS (TRPA1 agonists), or the neuropeptide substance P (SP), which is released from sensory nerve terminals by capsaicin, acrolein or CS), produced neurogenic inflammation in mouse airways. However, only acrolein and CS, but not capsaicin or SP, released the keratinocyte chemoattractant (CXCL-1/KC, IL-8 analogue) in bronchoalveolar lavage (BAL) fluid of wild-type mice. This effect of TRPA1 agonists was attenuated by TRPA1 antagonism or in TRPA1-deficient mice, but not by pharmacological ablation of sensory nerves. CONCLUSIONS: Our results demonstrate that, although either TRPV1 or TRPA1 activation causes airway neurogenic inflammation, solely TRPA1 activation orchestrates an additional inflammatory response which is not neurogenic. This finding suggests that non-neuronal TRPA1 in the airways is functional and potentially capable of contributing to inflammatory airway diseases. SN - 1932-6203 UR - https://www.unboundmedicine.com/medline/citation/22905134/Transient_receptor_potential_ankyrin_1_channel_localized_to_non_neuronal_airway_cells_promotes_non_neurogenic_inflammation_ L2 - https://dx.plos.org/10.1371/journal.pone.0042454 DB - PRIME DP - Unbound Medicine ER -