Granulysin expressed in a humanized mouse model induces apoptotic cell death and suppresses tumorigenicity
Journal
Oncotarget
Journal Volume
8
Journal Issue
48
Pages
83495
Date Issued
2017-01-01
Author(s)
Hsiao, Ya Wen
Lai, Tsung Ching
Lin, Yu Hsiang
Su, Chia Yi
Liao, Albert Taiching
Lin, Yuan Feng
Wu, Alexander T.H.
Abstract
© 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.
Subjects
Apoptosis | Granulysin | Humanized mouse model | Tumorigenicity
Apoptosis; Granulysin; Humanized mouse model; Tumorigenicity
Other Subjects
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
Publisher
IMPACT JOURNALS LLC
Type
journal article
File(s)![Thumbnail Image]()
Loading...
Name
11473-269357-10-PB.pdf
Size
8.34 MB
Format
Adobe PDF
Checksum
(MD5):8d6527863d516181e9045013ca7960f2