Platelet activating factor receptor regulates colitis-induced pulmonary inflammation through the NLRP3 inflammasome

Liu, G; Mateer, SW; Hsu, A; Goggins, BJ; Tay, H; Mathe, A; Fan, K; Neal, R; Bruce, J; Burns, G; Minahan, K; Maltby, S; Fricker, M; Foster, PS; Wark, PAB; Hansbro, PM; Keely, S

Platelet activating factor receptor regulates colitis-induced pulmonary inflammation through the NLRP3 inflammasome

Mateer, SW Hsu, A Goggins, BJ Tay, H Mathe, A Fan, K Neal, R Bruce, J Burns, G Minahan, K Maltby, S Fricker, M Foster, PS Wark, PAB Hansbro, PM

Keely, S

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Publication Type:: Journal Article
Citation:: Mucosal Immunology, 2019, 12 (4), pp. 862 - 873
Issue Date:: 2019-07-01

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Field	Value	Language
dc.contributor.author	Liu, G https://orcid.org/0000-0002-0489-2638	en_US
dc.contributor.author	Mateer, SW	en_US
dc.contributor.author	Hsu, A	en_US
dc.contributor.author	Goggins, BJ	en_US
dc.contributor.author	Tay, H	en_US
dc.contributor.author	Mathe, A	en_US
dc.contributor.author	Fan, K	en_US
dc.contributor.author	Neal, R	en_US
dc.contributor.author	Bruce, J	en_US
dc.contributor.author	Burns, G	en_US
dc.contributor.author	Minahan, K	en_US
dc.contributor.author	Maltby, S	en_US
dc.contributor.author	Fricker, M	en_US
dc.contributor.author	Foster, PS	en_US
dc.contributor.author	Wark, PAB	en_US
dc.contributor.author	Hansbro, PM https://orcid.org/0000-0002-4741-3035	en_US
dc.contributor.author	Keely, S	en_US
dc.date.available	2019-03-24	en_US
dc.date.issued	2019-07-01	en_US
dc.identifier.citation	Mucosal Immunology, 2019, 12 (4), pp. 862 - 873	en_US
dc.identifier.issn	1933-0219	en_US
dc.identifier.uri	http://hdl.handle.net/10453/132666
dc.description.abstract	© 2019, Society for Mucosal Immunology. Extra-intestinal manifestations (EIM) are common in inflammatory bowel disease (IBD). One such EIM is sub-clinical pulmonary inflammation, which occurs in up to 50% of IBD patients. In animal models of colitis, pulmonary inflammation is driven by neutrophilic infiltrations, primarily in response to the systemic bacteraemia and increased bacterial load in the lungs. Platelet activating factor receptor (PAFR) plays a critical role in regulating pulmonary responses to infection in conditions, such as chronic obstructive pulmonary disease and asthma. We investigated the role of PAFR in pulmonary EIMs of IBD, using dextran sulfate sodium (DSS) and anti-CD40 murine models of colitis. Both models induced neutrophilic inflammation, with increased TNF and IL-1β levels, bacterial load and PAFR protein expression in mouse lungs. Antagonism of PAFR decreased lung neutrophilia, TNF, and IL-1β in an NLRP3 inflammasome-dependent manner. Lipopolysaccharide from phosphorylcholine (ChoP)-positive bacteria induced NLRP3 and caspase-1 proteins in human alveolar epithelial cells, however antagonism of PAFR prevented NLRP3 activation by ChoP. Amoxicillin reduced bacterial populations in the lungs and reduced NLRP3 inflammasome protein levels, but did not reduce PAFR. These data suggest a role for PAFR in microbial pattern recognition and NLRP3 inflammasome signaling in the lung.	en_US
dc.relation	http://purl.org/au-research/grants/nhmrc/GNT1079187
dc.relation.ispartof	Mucosal Immunology	en_US
dc.relation.isbasedon	10.1038/s41385-019-0163-3	en_US
dc.subject.classification	Immunology	en_US
dc.title	Platelet activating factor receptor regulates colitis-induced pulmonary inflammation through the NLRP3 inflammasome	en_US
dc.type	Journal Article
utslib.citation.volume	4	en_US
utslib.citation.volume	12	en_US
utslib.for	1102 Cardiorespiratory Medicine and Haematology	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
utslib.copyright.status	open_access
pubs.issue	4	en_US
pubs.publication-status	Published	en_US
pubs.volume	12	en_US

Abstract:

© 2019, Society for Mucosal Immunology. Extra-intestinal manifestations (EIM) are common in inflammatory bowel disease (IBD). One such EIM is sub-clinical pulmonary inflammation, which occurs in up to 50% of IBD patients. In animal models of colitis, pulmonary inflammation is driven by neutrophilic infiltrations, primarily in response to the systemic bacteraemia and increased bacterial load in the lungs. Platelet activating factor receptor (PAFR) plays a critical role in regulating pulmonary responses to infection in conditions, such as chronic obstructive pulmonary disease and asthma. We investigated the role of PAFR in pulmonary EIMs of IBD, using dextran sulfate sodium (DSS) and anti-CD40 murine models of colitis. Both models induced neutrophilic inflammation, with increased TNF and IL-1β levels, bacterial load and PAFR protein expression in mouse lungs. Antagonism of PAFR decreased lung neutrophilia, TNF, and IL-1β in an NLRP3 inflammasome-dependent manner. Lipopolysaccharide from phosphorylcholine (ChoP)-positive bacteria induced NLRP3 and caspase-1 proteins in human alveolar epithelial cells, however antagonism of PAFR prevented NLRP3 activation by ChoP. Amoxicillin reduced bacterial populations in the lungs and reduced NLRP3 inflammasome protein levels, but did not reduce PAFR. These data suggest a role for PAFR in microbial pattern recognition and NLRP3 inflammasome signaling in the lung.

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http://hdl.handle.net/10453/132666