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Mer signaling increases the abundance of the transcription factor LXR to promote the resolution of acute sterile inflammation

Title
Mer signaling increases the abundance of the transcription factor LXR to promote the resolution of acute sterile inflammation
Authors
Choi, Ji-YeonSeo, Jeong YeonYoon, Young-SoLee, Ye-JiKim, Hee-SunKang, Jihee Lee
Ewha Authors
이지희김희선서정연
SCOPUS Author ID
이지희scopus; 김희선scopus
Issue Date
2015
Journal Title
SCIENCE SIGNALING
ISSN
1945-0877JCR Link1937-9145JCR Link
Citation
vol. 8, no. 365
Publisher
AMER ASSOC ADVANCEMENT SCIENCE
Indexed
SCIE WOS
Abstract
The receptor tyrosinekinaseMerplaysacentral role in inhibiting the inflammatory response of immunecells to pathogens. We aimed to understand the function of Mer signaling in the resolution of sterile inflammation in experiments with a Mer-neutralizing antibody or with Mer-deficient (Mer(-/-)) mice in a model of sterile, zymosan-induced acute inflammation. We found that inhibition or deficiency of Mer enhanced local and systemic inflammatory responses. The exacerbated inflammatory responses induced by the lack of Mer signaling were associated with reduced abundance of the transcription factors liver X receptor alpha (LXR alpha) and LXR beta and decreased expression of their target genes in peritoneal macrophages, spleens, and lungs. Similarly, treatment of mice with a Mer/Fc fusion protein, which prevents the Mer ligand Gas6 (growth arrest-specific protein 6) from binding to Mer, exacerbated the inflammatory response and decreased the abundance of LXR. Coadministration of the LXR agonist T0901317 with the Mer-neutralizing antibody inhibited the aggravating effects of the antibody on inflammation in mice. In vitro exposure of RAW264.7 cells or primary peritoneal macrophages to Gas6 increased LXR abundance in an Akt-dependent manner. Thus, we have elucidated a previously uncharacterized pathway involved in the resolution of acute sterile inflammation: EnhancedMer signaling during the recovery phase increases the abundance and activity of LXR to inactivate the inflammatory response in macrophages.
DOI
10.1126/scisignal.2005864
Appears in Collections:
의학전문대학원 > 의학과 > Journal papers
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