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IBD leads to a breakdown in the integrity of the intestinal barrier causing an increase in portal and systemic gut\u2010derived antigens, which challenge the liver. Here, we examined the role of platelet activating factor receptor (PAFR) in colitis\u2010associated liver damage using dextran sulfate sodium (DSS) and anti\u2010CD40\u2010induced colitis models. Both DSS and anti\u2010CD40 models exhibited liver inflammation associated with colitis. Colitis reduced global PAFR protein expression in mouse livers causing an exclusive re\u2010localization 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\u2010localized with toll\u2010like receptor 4. DSS activated the NLRP3\u2010inflammasome and increased interleukin (IL)\u20101\u03b2 in the liver. Antagonism of PAFR amplified the inflammasome response by increasing NLRP3, caspase\u20101, and IL\u20101\u03b2 protein levels in the liver. LPS also increased NLRP3 response in human hepatocytes, however, overexpression of PAFR restored the levels of NLPR3 and caspase\u20101 proteins. Interestingly, KCs depletion also increased IL\u20101\u03b2 protein in mouse liver after DSS challenge. These data suggest a protective role for PAFR\u2010expressing KCs during colitis and that regulation of PAFR is important for gut\u2010liver axis homeostasis.<\/jats:p>","DOI":"10.1096\/fj.201901779r","type":"journal-article","created":{"date-parts":[[2020,4,15]],"date-time":"2020-04-15T11:55:50Z","timestamp":1586951750000},"page":"7718-7732","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Platelet activating factor receptor acts to limit colitis\u2010induced liver inflammation"],"prefix":"10.1096","volume":"34","author":[{"given":"Gang","family":"Liu","sequence":"first","affiliation":[{"name":"Priority Research Centre for Digestive Health and Neurogastroenterology The University of Newcastle Newcastle NSW Australia"},{"name":"Hunter Medical Research Institute New Lambton Heights NSW Australia"},{"name":"School of Biomedical Sciences and Pharmacy Faculty of Health and Medicine The University of Newcastle Callaghan 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M.","family":"Nair","sequence":"additional","affiliation":[{"name":"Priority Research Centre for Digestive Health and Neurogastroenterology The University of Newcastle Newcastle NSW Australia"},{"name":"Hunter Medical Research Institute New Lambton Heights NSW Australia"},{"name":"School of Biomedical Sciences and Pharmacy Faculty of Health and Medicine The University of Newcastle Callaghan NSW Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samwel","family":"Makanyengo","sequence":"additional","affiliation":[{"name":"Priority Research Centre for Digestive Health and Neurogastroenterology The University of Newcastle Newcastle NSW Australia"},{"name":"Hunter Medical Research Institute New Lambton Heights NSW Australia"},{"name":"School of Biomedical Sciences and Pharmacy Faculty of Health and Medicine The University of Newcastle Callaghan NSW 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The University of Newcastle Newcastle NSW Australia"},{"name":"Hunter Medical Research Institute New Lambton Heights NSW Australia"},{"name":"School of Biomedical Sciences and Pharmacy Faculty of Health and Medicine The University of Newcastle Callaghan NSW Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hock","family":"Tay","sequence":"additional","affiliation":[{"name":"Hunter Medical Research Institute New Lambton Heights NSW Australia"},{"name":"School of Biomedical Sciences and Pharmacy Faculty of Health and Medicine The University of Newcastle Callaghan NSW Australia"},{"name":"Priority Research Centre for Healthy Lungs The University of Newcastle Newcastle NSW Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Mathe","sequence":"additional","affiliation":[{"name":"Priority Research Centre for Digestive Health and Neurogastroenterology The University of Newcastle Newcastle NSW Australia"},{"name":"Hunter Medical 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