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논문 기본 정보
- 자료유형
- 학술저널
- 저자정보
- 발행연도
- 2020.1
- 수록면
- 402 - 411 (10page)
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Background/Aims: The modulation of CD1d-restricted natural killer T (NKT) cells by glycolipids has been considered as a potential therapy against immunologic diseases, including inflammatory bowel disease. A recently identified a glycolipid analog, 7DW8-5, which is derived from α-galactosylceramide (α-GalCer), is as much as 100-fold more active at stimulating both human and mice NKT cells when compared to α-GalCer. We explored the effects of 7DW8-5 in mouse models of acute and chronic colitis.Methods: We investigated the effects of 7DW8-5 on intestinal inflammation by assessing the effects of 7dW8-5 on a murine dextran sulfate sodium (DSS)-induced acute colitis model and a chronic colitis-associated tumor model.Results: The acute DSS-induced colitis model showed a dose-dependent response to 7DW8-5, as mice administered 7DW8-5 showed a significant improvement in DSS-induced colitis based on their disease activity index, histologic analysis, and serum C-reactive protein levels, when compared to mice administered vehicle alone. However, DSS-induced colitis in CD1d-KO mice showed no response to 7DW8-5. A fluorescence-activating cell sorting analysis revealed an increase in NKT cells in colonic tissues of 7DW8-5-treated mice. RNA-seq and real-time quantitative polymerase chain reaction showed a significant increase in the expression of interleukin (IL)-4, IL-13, and interferon-gamma in 7DW8-5-treated mice. In addition, 7DW8-5 treatment reduced colitis-associated tumor development in an azoxymethane/DSS mouse model.Conclusions: 7DW8-5 activates NKT cells through CD1d and provides a protective effect against intestinal inflammation in mice. Therefore, 7DW8-5 may be a promising therapeutic agent for treatment of inflammatory bowel disease.
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참고문헌 (27)
참고문헌 신청
Carreño LJ / 2016 / Synthetic glycolipid activators of natural killer T cells as immunotherapeutic agents / Clin Transl Immunology 5:e69
van Dieren JM / 2007 / Roles of CD1d-restricted NKT cells in the intestine / Inflamm Bowel Dis 13:1146~1152
Terabe M / 2008 / The role of NKT cells in tumor immunity / Adv Cancer Res 101:277~348
Middendorp S / 2009 / NKT cells in mucosal immunity / Mucosal Immunol 2:393~402
Tefit JN / 2010 / NKT cell responses to glycolipid activation / Methods Mol Biol 626:149~167
van Dieren JM / 2007 / Roles of CD1d-restricted NKT cells in the intestine / Inflamm Bowel Dis 13:1146~1152
Terabe M / 2008 / The role of NKT cells in tumor immunity / Adv Cancer Res 101:277~348
Middendorp S / 2009 / NKT cells in mucosal immunity / Mucosal Immunol 2:393~402
Tefit JN / 2010 / NKT cell responses to glycolipid activation / Methods Mol Biol 626:149~167
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