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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-Yoon; Lim, Eun-Jin; Yoon, Young-So; Ahn, Young-Ho; Park, Eun-Mi; Kim, Hee-Sun; Kang, Jihee Lee
- Ewha Authors
- 이지희; 김희선; 박은미; 임은진; 안영호
- SCOPUS Author ID
- 이지희; 김희선; 박은미; 안영호
- Issue Date
- 2016
- Journal Title
- SCIENTIFIC REPORTS
- ISSN
- 2045-2322
- Citation
- SCIENTIFIC REPORTS vol. 6
- Publisher
- NATURE PUBLISHING GROUP
- Indexed
- SCIE; SCOPUS
- Document Type
- Article
- 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
- Appears in Collections:
- 의과대학 > 의학과 > Journal papers
- Files in This Item:
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