- Title
- Platelet activating factor receptor regulates colitis-induced pulmonary inflammation through the NLRP3 inflammasome
- Creator
- Liu, Gang; Mateer, Sean W.; Minahan, Kyra; Maltby, Steven; Fricker, Michael; Foster, Paul S.; Wark, Peter A. B.; Hansbro, Philip M.; Keely, Simon; Hsu, Alan; Goggins, Bridie J.; Tay, Hock; Mathe, Andrea; Fan, Kening; Neal, Rachel; Bruce, Jessica; Burns, Grace
- Relation
- Mucosal Immunology Vol. 12, Issue 4, p. 862-873
- Publisher Link
- http://dx.doi.org/10.1038/s41385-019-0163-3
- Publisher
- Elsevier
- Resource Type
- journal article
- Date
- 2019
- Description
- 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.
- Subject
- extra-intestinal manifestations (EIM); inflammatory bowel disease (IBD); pulmonary; lungs; SDG 3; Sustainable Development Goals
- Identifier
- http://hdl.handle.net/1959.13/1470932
- Identifier
- uon:48579
- Identifier
- ISSN:1933-0219
- Language
- eng
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