한빛사 논문
- 조회358
Eui-Soon Park 1,†, Hyoeun Jeon 1,†, Nari Lee 1, Jiyeon Yu 1, Hye-Won Park 1, Takashi Satoh 2, Shizuo Akira 3, Tatsuo Furuyama 4, Chul-Ho Lee 5, Jong-Soon Choi 6 and Jaerang Rho *,1
1Department of Microbiology and Molecular Biology, Chungnam National University, Daejeon, Korea
2Department of Immune Regulation, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan
3Laboratory of Host Defense, WPI Immunology Frontier Research Center, Osaka University, Osaka, Japan
4Department of Molecular Genetics and Geriatric Research, National Institute for Longevity Sciences, Kumamoto University, Kumamoto, Japan
5Laboratory Animal Center, Korea Research Institute of Bioscience & Biotechnology (KRIBB), Daejeon, Korea
6Division of Life Science, Korea Basic Science Institute (KBSI), Daejeon, Korea
†These authors contributed equally to this work
*Corresponding author: correspondence to Jaerang Rho
Abstract
Tight regulation of Toll-like receptor (TLR)-mediated inflammatory responses is important for innate immunity. Here, we show that T-cell death-associated gene 51 (TDAG51/PHLDA1) is a novel regulator of the transcription factor FoxO1, regulating inflammatory mediator production in the lipopolysaccharide (LPS)-induced inflammatory response. TDAG51 induction by LPS stimulation was mediated by the TLR2/4 signaling pathway in bone marrow-derived macrophages (BMMs). LPS-induced inflammatory mediator production was significantly decreased in TDAG51-deficient BMMs. In TDAG51-deficient mice, LPS- or pathogenic Escherichia coli infection-induced lethal shock was reduced by decreasing serum proinflammatory cytokine levels. The recruitment of 14-3-3ζ to FoxO1 was competitively inhibited by the TDAG51-FoxO1 interaction, leading to blockade of FoxO1 cytoplasmic translocation and thereby strengthening FoxO1 nuclear accumulation. TDAG51/FoxO1 double-deficient BMMs showed significantly reduced inflammatory mediator production compared with TDAG51- or FoxO1-deficient BMMs. TDAG51/FoxO1 double deficiency protected mice against LPS- or pathogenic E. coli infection-induced lethal shock by weakening the systemic inflammatory response. Thus, these results indicate that TDAG51 acts as a regulator of the transcription factor FoxO1, leading to strengthened FoxO1 activity in the LPS-induced inflammatory response.
논문정보
- Research article
- 2023년 07월 (BRIC 등록일 2023-05-25)
- 국내(교신)+국외 연구진
- 생명과학 > 면역학
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