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Liver X receptor and STAT1 cooperate downstream of Gas6/Mer to induce anti-inflammatory arginase 2 expression in macrophages

Title
Liver X receptor and STAT1 cooperate downstream of Gas6/Mer to induce anti-inflammatory arginase 2 expression in macrophages
Authors
Kim, Si-YoonLim, Eun-JinYoon, Young-SoAhn, Young-HoPark, Eun-MiKim, Hee-SunKang, Jihee Lee
Ewha Authors
이지희김희선박은미임은진안영호
SCOPUS Author ID
이지희scopus; 김희선scopus; 박은미scopus; 안영호scopus
Issue Date
2016
Journal Title
SCIENTIFIC REPORTS
ISSN
2045-2322JCR Link
Citation
vol. 6
Publisher
NATURE PUBLISHING GROUP
Indexed
SCI; SCIE; SCOPUS WOS scopus
Abstract
Mer signaling increases the transcriptional activity of liver X receptor (LXR) to promote the resolution of acute sterile inflammation. Here, we aimed to understand the pathway downstream of Mer signaling after growth arrest-specific protein 6 (Gas6) treatment that leads to LXR expression and transcriptional activity in mouse bone-marrow derived macrophages (BMDM). Gas6-induced increases in LXR alpha and LXR beta and expression of their target genes were inhibited in BMDM from STAT1(-/-) mice or by the STAT1-specific inhibitor fludarabine. Gas6-induced STAT1 phosphorylation, LXR activation, and LXR target gene expression were inhibited in BMDM from Mer(-/-) mice or by inhibition of PI3K or Akt. Gas6-induced Akt phosphorylation was inhibited in BMDM from STAT1(-/-) mice or in the presence of fludarabine. Gas6-induced LXR activity was enhanced through an interaction between LXRa and STAT1 on the DNA promoter of Arg2. Additionally, we found that Gas6 inhibited lipopolysaccharide (LPS)-induced nitrite production in a STAT1 and LXR pathway-dependent manner in BMDM. Additionally, Mer-neutralizing antibody reduced LXR and Arg2 expression in lung tissue and enhanced NO production in bronchoalveolar lavage fluid in LPS-induced acute lung injury. Our data suggest the possibility that the Gas6-Mer-PI3K/Akt-STAT1-LXR-Arg2 pathway plays an essential role for resolving inflammatory response in acute lung injury.
DOI
10.1038/srep29673
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의학전문대학원 > 의학과 > Journal papers
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