Mucosal production of uric acid by airway epithelial cells contributes to particulate matter-induced allergic sensitization

Gold, MJ; Hiebert, PR; Park, HY; Stefanowicz, D; Le, A; Starkey, MR; Deane, A; Brown, AC; Liu, G; Horvat, JC; Ibrahim, ZA; Sukkar, MB; Hansbro, PM; Carlsten, C; Vaneeden, S; Sin, DD; McNagny, KM; Knight, DA; Hirota, JA

Mucosal production of uric acid by airway epithelial cells contributes to particulate matter-induced allergic sensitization

Gold, MJ Hiebert, PR Park, HY Stefanowicz, D Le, A Starkey, MR Deane, A Brown, AC Liu, G

Horvat, JC Ibrahim, ZA

Sukkar, MB

Hansbro, PM

Carlsten, C Vaneeden, S Sin, DD McNagny, KM Knight, DA Hirota, JA

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Publication Type:: Journal Article
Citation:: Mucosal Immunology, 2016, 9 (3), pp. 809 - 820
Issue Date:: 2016-05-01

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Field	Value	Language
dc.contributor.author	Gold, MJ	en_US
dc.contributor.author	Hiebert, PR	en_US
dc.contributor.author	Park, HY	en_US
dc.contributor.author	Stefanowicz, D	en_US
dc.contributor.author	Le, A	en_US
dc.contributor.author	Starkey, MR	en_US
dc.contributor.author	Deane, A	en_US
dc.contributor.author	Brown, AC	en_US
dc.contributor.author	Liu, G https://orcid.org/0000-0002-0489-2638	en_US
dc.contributor.author	Horvat, JC	en_US
dc.contributor.author	Ibrahim, ZA https://orcid.org/0000-0001-7829-2160	en_US
dc.contributor.author	Sukkar, MB https://orcid.org/0000-0003-4591-2399	en_US
dc.contributor.author	Hansbro, PM https://orcid.org/0000-0002-4741-3035	en_US
dc.contributor.author	Carlsten, C	en_US
dc.contributor.author	Vaneeden, S	en_US
dc.contributor.author	Sin, DD	en_US
dc.contributor.author	McNagny, KM	en_US
dc.contributor.author	Knight, DA	en_US
dc.contributor.author	Hirota, JA	en_US
dc.date.available	2015-09-03	en_US
dc.date.issued	2016-05-01	en_US
dc.identifier.citation	Mucosal Immunology, 2016, 9 (3), pp. 809 - 820	en_US
dc.identifier.issn	1933-0219	en_US
dc.identifier.uri	http://hdl.handle.net/10453/74189
dc.description.abstract	Exposure to particulate matter (PM), a major component of air pollution, contributes to increased morbidity and mortality worldwide. PM induces innate immune responses and contributes to allergic sensitization, although the mechanisms governing this process remain unclear. Lung mucosal uric acid has also been linked to allergic sensitization. The links among PM exposure, uric acid, and allergic sensitization remain unexplored. We therefore investigated the mechanisms behind PM-induced allergic sensitization in the context of lung mucosal uric acid. PM 10 and house dust mite exposure selectively induced lung mucosal uric acid production and secretion in vivo, which did not occur with other challenges (lipopolysaccharide, virus, bacteria, or inflammatory/fibrotic stimuli). PM 10 -induced uric acid mediates allergic sensitization and augments antigen-specific T-cell proliferation, which is inhibited by uricase. We then demonstrate that human airway epithelial cells secrete uric acid basally and after stimulation through a previously unidentified mucosal secretion system. Our work discovers a previously unknown mechanism of air pollution-induced, uric acid-mediated, allergic sensitization that may be important in the pathogenesis of asthma.	en_US
dc.relation.ispartof	Mucosal Immunology	en_US
dc.relation.isbasedon	10.1038/mi.2015.104	en_US
dc.subject.classification	Immunology	en_US
dc.subject.mesh	Lung	en_US
dc.subject.mesh	Respiratory Mucosa	en_US
dc.subject.mesh	T-Lymphocytes	en_US
dc.subject.mesh	Cells, Cultured	en_US
dc.subject.mesh	Animals	en_US
dc.subject.mesh	Mice, Inbred C57BL	en_US
dc.subject.mesh	Mice, Knockout	en_US
dc.subject.mesh	Humans	en_US
dc.subject.mesh	Mice	en_US
dc.subject.mesh	Pyroglyphidae	en_US
dc.subject.mesh	Hypersensitivity	en_US
dc.subject.mesh	Uric Acid	en_US
dc.subject.mesh	Antigens, Dermatophagoides	en_US
dc.subject.mesh	Immunization	en_US
dc.subject.mesh	Environmental Exposure	en_US
dc.subject.mesh	Cell Proliferation	en_US
dc.subject.mesh	Immunity, Mucosal	en_US
dc.subject.mesh	Female	en_US
dc.subject.mesh	Particulate Matter	en_US
dc.subject.mesh	Toll-Like Receptor 4	en_US
dc.title	Mucosal production of uric acid by airway epithelial cells contributes to particulate matter-induced allergic sensitization	en_US
dc.type	Journal Article
utslib.citation.volume	3	en_US
utslib.citation.volume	9	en_US
utslib.for	1115 Pharmacology and Pharmaceutical Sciences	en_US
utslib.for	06 Biological Sciences	en_US
utslib.for	11 Medical and Health Sciences	en_US
pubs.embargo.period	Not known	en_US
pubs.organisational-group	/University of Technology Sydney
pubs.organisational-group	/University of Technology Sydney/Faculty of Science
pubs.organisational-group	/University of Technology Sydney/Faculty of Science/School of Life Sciences
pubs.organisational-group	/University of Technology Sydney/Graduate School of Health
utslib.copyright.status	closed_access
pubs.issue	3	en_US
pubs.publication-status	Published	en_US
pubs.volume	9	en_US

Abstract:

Exposure to particulate matter (PM), a major component of air pollution, contributes to increased morbidity and mortality worldwide. PM induces innate immune responses and contributes to allergic sensitization, although the mechanisms governing this process remain unclear. Lung mucosal uric acid has also been linked to allergic sensitization. The links among PM exposure, uric acid, and allergic sensitization remain unexplored. We therefore investigated the mechanisms behind PM-induced allergic sensitization in the context of lung mucosal uric acid. PM 10 and house dust mite exposure selectively induced lung mucosal uric acid production and secretion in vivo, which did not occur with other challenges (lipopolysaccharide, virus, bacteria, or inflammatory/fibrotic stimuli). PM 10 -induced uric acid mediates allergic sensitization and augments antigen-specific T-cell proliferation, which is inhibited by uricase. We then demonstrate that human airway epithelial cells secrete uric acid basally and after stimulation through a previously unidentified mucosal secretion system. Our work discovers a previously unknown mechanism of air pollution-induced, uric acid-mediated, allergic sensitization that may be important in the pathogenesis of asthma.

Please use this identifier to cite or link to this item:

http://hdl.handle.net/10453/74189