- Title
- Platelet activating factor receptor acts to limit colitis-induced liver inflammation
- Creator
- Liu, Gang; Baird, Alan W.; Tay, Hock; Mathe, Andrea; Soh, Wai S.; Minahan, Kyra; Hansbro, Phil M.; Nixon, Brett; McCaughan, Geoffrey W.; Holtmann, Gerald; Colgan, Sean P.; Keely, Simon; Parsons, Marie J.; Fan, Kening; Skerrett-Byrne, David A.; Nair, Prema M.; Makanyengo, Samwel; Chen, Jinbiao; Neal, Rachel; Goggins, Bridie J.
- Relation
- NHMRC.APP1128487 http://purl.org/au-research/grants/nhmrc/1128487
- Relation
- FASEB Journal Vol. 34, Issue 6, p. 7718-7732
- Publisher Link
- http://dx.doi.org/10.1096/fj.201901779R
- Publisher
- Wiley-Blackwell
- Resource Type
- journal article
- Date
- 2020
- Description
- Liver inflammation is a common extraintestinal manifestation in inflammatory bowel disease (IBD), yet, the mechanisms driving gut-liver axis inflammation remain poorly understood. IBD leads to a breakdown in the integrity of the intestinal barrier causing an increase in portal and systemic gut-derived antigens, which challenge the liver. Here, we examined the role of platelet activating factor receptor (PAFR) in colitis-associated liver damage using dextran sulfate sodium (DSS) and anti-CD40-induced colitis models. Both DSS and anti-CD40 models exhibited liver inflammation associated with colitis. Colitis reduced global PAFR protein expression in mouse livers causing an exclusive re-localization of PAFR to the portal triad. The global decrease in liver PAFR was associated with increased sirtuin 1 while relocalized PAFR expression was limited to Kupffer cells (KCs) and co-localized with toll-like receptor 4. DSS activated the NLRP3-inflammasome and increased interleukin (IL)-1β in the liver. Antagonism of PAFR amplified the inflammasome response by increasing NLRP3, caspase-1, and IL-1β protein levels in the liver. LPS also increased NLRP3 response in human hepatocytes, however, overexpression of PAFR restored the levels of NLPR3 and caspase-1 proteins. Interestingly, KCs depletion also increased IL-1β protein in mouse liver after DSS challenge. These data suggest a protective role for PAFR-expressing KCs during colitis and that regulation of PAFR is important for gut-liver axis homeostasis.
- Subject
- extraintestinal manifestations in liver; inflammatory bowel disease; PAFR
- Identifier
- http://hdl.handle.net/1959.13/1443387
- Identifier
- uon:41982
- Identifier
- ISSN:0892-6638
- Language
- eng
- Reviewed
- Hits: 3913
- Visitors: 3903
- Downloads: 0
| Thumbnail | File | Description | Size | Format |
|---|