Journal article
Activation of the immune-metabolic receptor GPR84 enhances inflammation and phagocytosis in macrophages
- Abstract:
- GPR84 is a member of the metabolic G protein-coupled receptor family, and its expression has been described predominantly in immune cells. GPR84 activation is involved in the inflammatory response, but the mechanisms by which it modulates inflammation have been incompletely described. In this study, we investigated GPR84 expression, activation, and function in macrophages to establish the role of the receptor during the inflammatory response. We observed that GPR84 expression in murine tissues is increased by endotoxemia, hyperglycemia, and hypercholesterolemia. Ex vivo studies revealed that GPR84 mRNA expression is increased by LPS and other pro-inflammatory molecules in different murine and human macrophage populations. Likewise, high glucose concentrations and the presence of oxidized LDL increased GPR84 expression in macrophages. Activation of the GPR84 receptor with a selective agonist, 6-(octylamino) pyrimidine-2,4(1H,3H)-dione (6-n-octylaminouracil, 6-OAU), enhanced the expression of phosphorylated Akt, p-ERK, and p65 nuclear translocation under inflammatory conditions and elevated the expression levels of the inflammatory mediators TNFa, IL-6, IL-12B, CCL2, CCL5, and CXCL1. In addition, GPR84 activation triggered increased bacterial adhesion and phagocytosis in macrophages. The enhanced inflammatory response mediated by 6-OAU was not observed in GPR84-/-cells nor in macrophages treated with a selective GPR84 antagonist. Collectively, our results reveal that GPR84 functions as an enhancer of inflammatory signaling in macrophages once inflammation is established. Therefore, molecules that antagonize the GPR84 receptor may be potential therapeutic tools in inflammatory and metabolic diseases.
- Publication status:
- Published
- Peer review status:
- Peer reviewed
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Authors
- Publisher:
- Frontiers Media
- Journal:
- Frontiers in Immunology More from this journal
- Volume:
- 9
- Issue:
- JUN
- Pages:
- 1419
- Publication date:
- 2018-06-20
- Acceptance date:
- 2018-06-06
- DOI:
- EISSN:
-
1664-3224
- ISSN:
-
1664-3224
- Keywords:
- Pubs id:
-
pubs:858734
- UUID:
-
uuid:e8c8ebe3-aa28-4074-b277-7e6906394da6
- Local pid:
-
pubs:858734
- Deposit date:
-
2018-07-03
Terms of use
- Copyright holder:
- Monaco et al
- Copyright date:
- 2018
- Notes:
- Copyright © 2018 Recio, Lucy, Purvis, Iveson, Zeboudj, Iqbal, Lin, O’Callaghan, Davison, Griesbach, Russell, Wynne, Dib, Monaco and Greaves. This is an openaccess article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
- Licence:
- CC Attribution (CC BY)
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