In:
Scientific Reports, Springer Science and Business Media LLC, Vol. 8, No. 1 ( 2018-10-10)
Abstract:
The expression of chemokine receptor CX 3 CR1 is related to migration and signaling in cells of the monocyte-macrophage lineage. The precise roles of CX 3 CR1 in the liver have been investigated but not clearly elucidated. Here, we investigated the roles of CX 3 CR1 in hepatic macrophages and liver injury. Hepatic and splenic CX 3 CR1 low F4/80 low monocytes and CX 3 CR1 low CD16 − monocytes were differentiated into CX 3 CR1 high F4/80 high or CX 3 CR1 high CD16 + macrophages by co-culture with endothelial cells. Moreover, CX 3 CL1 deficiency in human umbilical vein endothelial cells (HUVECs) attenuated the expression of interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α), whereas recombinant CX 3 CL1 treatment reversed this expression in co-cultured monocytes. Upon treatment with clodronate liposome, hepatic F4/80 high macrophages were successfully depleted at day 2 and recovered similarly in CX 3 CR1 +/GFP and CX 3 CR1 GFP/GFP mice at week 4, suggesting a CX 3 CR1-independent replacement. However, F4/80 high macrophages of CX 3 CR1 +/GFP showed a stronger pro-inflammatory phenotype than CX 3 CR1 GFP/GFP mice. In clodronate-treated chimeric CX 3 CR1 +/GFP and CX 3 CR1 GFP/GFP mice, CX 3 CR1 + F4/80 high macrophages showed higher expression of IL-1β and TNF-α than CX 3 CR1 − F4/80 high macrophages. In alcoholic liver injury, despite the similar frequency of hepatic F4/80 high macrophages, CX 3 CR1 GFP/GFP mice showed reduced liver injury, hepatic fat accumulation, and inflammatory responses than CX 3 CR1 +/GFP mice. Thus, CX 3 CR1 could be a novel therapeutic target for pro-inflammatory macrophage-mediated liver injury.
Type of Medium:
Online Resource
ISSN:
2045-2322
DOI:
10.1038/s41598-018-33440-9
Language:
English
Publisher:
Springer Science and Business Media LLC
Publication Date:
2018
detail.hit.zdb_id:
2615211-3
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