Platelet activating factor receptor acts to limit colitis‐induced liver inflammation

Platelet activating factor receptor acts to limit colitis‐induced liver inflammation.

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Item Type: Article
Status: Published
Official URL: https://doi.org/10.1096/fj.201901779R
Journal or Publication Title: The FASEB Journal
Volume: 34
Number: 6
Page Range: pp. 7718-7732
Date: 2020
Divisions: Liver Injury and Cancer
UTS Centre for Inflammation
Depositing User: General Admin
Identification Number: 10.1096/fj.201901779R
ISSN: 0892-6638
Date Deposited: 04 Jan 2021 02:42
Abstract:

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.

Creators:
Creators
Email
Liu, Gang
UNSPECIFIED
Baird, Alan W.
UNSPECIFIED
Parsons, Marie J.
UNSPECIFIED
Fan, Kening
UNSPECIFIED
Skerrett‐Byrne, David A.
UNSPECIFIED
Nair, Prema M.
UNSPECIFIED
Makanyengo, Samwel
UNSPECIFIED
Chen, Jinbiao
UNSPECIFIED
Neal, Rachel
UNSPECIFIED
Goggins, Bridie J.
UNSPECIFIED
Tay, Hock
UNSPECIFIED
Mathe, Andrea
UNSPECIFIED
Soh, Wai S.
UNSPECIFIED
Minahan, Kyra
UNSPECIFIED
Hansbro, Phil M.
UNSPECIFIED
Nixon, Brett
UNSPECIFIED
McCaughan, Geoffrey W.
UNSPECIFIED
Holtmann, Gerald
UNSPECIFIED
Colgan, Sean P.
UNSPECIFIED
Keely, Simon
UNSPECIFIED
Last Modified: 04 Jan 2021 02:42
URI: https://eprints.centenary.org.au/id/eprint/767

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