https://scholars.lib.ntu.edu.tw/handle/123456789/414008
標題: | Granulysin expressed in a humanized mouse model induces apoptotic cell death and suppresses tumorigenicity | 作者: | Hsiao, Ya Wen Lai, Tsung Ching Lin, Yu Hsiang Su, Chia Yi JIH-JONG LEE Liao, Albert Taiching Lin, Yuan Feng SHU-CHEN HSIEH Wu, Alexander T.H. TAI-CHING LIAO |
關鍵字: | Apoptosis | Granulysin | Humanized mouse model | Tumorigenicity;Apoptosis; Granulysin; Humanized mouse model; Tumorigenicity | 公開日期: | 1-一月-2017 | 出版社: | IMPACT JOURNALS LLC | 卷: | 8 | 期: | 48 | 起(迄)頁: | 83495 | 來源出版物: | Oncotarget | 摘要: | © Hsiao et al. Granulysin (GNLY) is a cytolytic and proinflammatory protein expressed in activated human cytotoxic T lymphocytes (CTLs) and natural killer (NK) cells. Conventional mouse models cannot adequately address the triggering mechanism and immunopathological pathways in GNLY-associated diseases due to lack of the GNLY gene in the mouse genome. Therefore, we generated a humanized immune system (HIS) mouse model by transplanting human umbilical cord blood mononuclear cells into NOD.Cg-Prkdc scid Il2rg tm1Wjl /SzJ (NSG) mice after sublethally irradiation. We examined the GNLY expression and its effects on tumor growth using this system. Our HIS mice expressed human CD45 + , CD4 + , CD8 + and CD56 + cells in the peripheral blood and spleen. A high expression level of human Th1/Th2 and NK cytokines was detected, indicating the activation of both T and NK cells. Importantly, we found an elevated level of GNLY in the serum and it was produced by human CTLs and NK cells obtained from the peripheral blood mononuclear cells and spleen cells in the HIS mice. The serum level of GNLY was negatively correlated with the proliferation of transplanted tumor cells in HIS mice. Collectively, our findings strongly supported that HIS mouse as a valuable model for studying human cancer under an intact immune system and the role of GNLY in tumorigenesis. |
URI: | https://scholars.lib.ntu.edu.tw/handle/123456789/414008 | ISSN: | 1949-2553 | DOI: | https://api.elsevier.com/content/abstract/scopus_id/85031023048 10.18632/oncotarget.11473 |
SDG/關鍵字: | caspase 3; caspase 7; CD4 antigen; CD45 antigen; CD56 antigen; CD8 antigen; gamma interferon; granulysin; interleukin 10; interleukin 2; interleukin 5; nicotinamide adenine dinucleotide adenosine diphosphate ribosyltransferase; tumor necrosis factor; animal experiment; animal model; animal tissue; apoptosis; Article; carcinogenicity; cell proliferation; controlled study; cytokine production; cytotoxic T lymphocyte; human; human cell; mouse; mouse model; natural killer cell; NOD SCID gamma mouse; nonhuman; peripheral blood mononuclear cell; spleen cell; T lymphocyte activation; tumor growth |
顯示於: | 食品科技研究所 |
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11473-269357-10-PB.pdf | 8.54 MB | Adobe PDF | 檢視/開啟 |
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