Immunomodulatory Effects of Rhaphidophora Korthalsii Methanol Extract on Natural Killer Cell Activation and Cytolytic Activity

Rhaphidophora korthalsii (Araceae) is a root-climber plant which has been previously identified as splenocyte immunostimulator. The purpose of this study was to examine the in vitro and in vivo immunomodulatory effect of R. korthalsii methanol extract on immune cell proliferation, cytokine expres...

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Main Author:	Yeap, Swee Keong
Format:	Thesis
Language:	English English
Published:	2010
Subjects:	Immunological adjuvants Araceae
Online Access:	http://psasir.upm.edu.my/id/eprint/9835/1/FBSB_2010_2_A.pdf
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id	my-upm-ir.9835
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spelling	my-upm-ir.98352013-05-27T07:43:56Z Immunomodulatory Effects of Rhaphidophora Korthalsii Methanol Extract on Natural Killer Cell Activation and Cytolytic Activity 2010-01 Yeap, Swee Keong Rhaphidophora korthalsii (Araceae) is a root-climber plant which has been previously identified as splenocyte immunostimulator. The purpose of this study was to examine the in vitro and in vivo immunomodulatory effect of R. korthalsii methanol extract on immune cell proliferation, cytokine expression and cytotoxicity. More specifically, immunomodulatory effects of R. korthalsii methanol extract on the stimulation of NK cells activity and cytotoxicity against HepG2 monolayer and spheroid culture were determined. Immune cells [peripheral blood mononuclear cells (PBMC) and mice splenocytes] treated with this extract resulted in stimulation of cell proliferation, cytokine expression and cytotoxicity in dose and time dependent manner. For the in vivo immunostimulatory effect study, unlike rIL-2 which degraded rapidly, the stimulatory effect from the extract managed to last until day 15. In order to understand the activation of NK cells by R. korthalsii methanol extract, NK cells were treated directly or indirectly. Both direct and indirect stimulated NK cells showed high-level expression of cell surface FasL, NKG2D, 16B4 and extra-cellular IFN-γ and TNF-α. These activations contributed to the killing of NK cells against HepG2 monolayer cells through Granzyme B mitochondria caspases dependent secretory apoptosis pathway where DNA fragmentation, phosphatidylserine (PS) externalisation, caspase 3, caspase 8, caspase 9 up-regulation and XIAP, Bid downregulation were observed. Apart from that, extract stimulated NK cells which caused cell death on the HepG2 spheroid and inhibited the HepG2 cell invasion, suggesting that R. korthalsii methanol extract was a potential agent to inhibit liver tumour metastasis. Our findings indicated a potential IL-2 free immunotherapy through direct and indirect R. korthalsii activation on NK cells which can further induce apoptosis on the HepG2 monolayer and spheroid culture. Immunological adjuvants Araceae Cytotoxicity, Immunologic 2010-01 Thesis http://psasir.upm.edu.my/id/eprint/9835/ http://psasir.upm.edu.my/id/eprint/9835/1/FBSB_2010_2_A.pdf application/pdf en public phd doctoral Universiti Putra Malaysia Immunological adjuvants Araceae Cytotoxicity, Immunologic Faculty Biotechnology and Biomolecular Sciences English
institution	Universiti Putra Malaysia
collection	PSAS Institutional Repository
language	English English
topic	Immunological adjuvants Araceae Immunological adjuvants
spellingShingle	Immunological adjuvants Araceae Immunological adjuvants Yeap, Swee Keong Immunomodulatory Effects of Rhaphidophora Korthalsii Methanol Extract on Natural Killer Cell Activation and Cytolytic Activity
description	Rhaphidophora korthalsii (Araceae) is a root-climber plant which has been previously identified as splenocyte immunostimulator. The purpose of this study was to examine the in vitro and in vivo immunomodulatory effect of R. korthalsii methanol extract on immune cell proliferation, cytokine expression and cytotoxicity. More specifically, immunomodulatory effects of R. korthalsii methanol extract on the stimulation of NK cells activity and cytotoxicity against HepG2 monolayer and spheroid culture were determined. Immune cells [peripheral blood mononuclear cells (PBMC) and mice splenocytes] treated with this extract resulted in stimulation of cell proliferation, cytokine expression and cytotoxicity in dose and time dependent manner. For the in vivo immunostimulatory effect study, unlike rIL-2 which degraded rapidly, the stimulatory effect from the extract managed to last until day 15. In order to understand the activation of NK cells by R. korthalsii methanol extract, NK cells were treated directly or indirectly. Both direct and indirect stimulated NK cells showed high-level expression of cell surface FasL, NKG2D, 16B4 and extra-cellular IFN-γ and TNF-α. These activations contributed to the killing of NK cells against HepG2 monolayer cells through Granzyme B mitochondria caspases dependent secretory apoptosis pathway where DNA fragmentation, phosphatidylserine (PS) externalisation, caspase 3, caspase 8, caspase 9 up-regulation and XIAP, Bid downregulation were observed. Apart from that, extract stimulated NK cells which caused cell death on the HepG2 spheroid and inhibited the HepG2 cell invasion, suggesting that R. korthalsii methanol extract was a potential agent to inhibit liver tumour metastasis. Our findings indicated a potential IL-2 free immunotherapy through direct and indirect R. korthalsii activation on NK cells which can further induce apoptosis on the HepG2 monolayer and spheroid culture.
format	Thesis
qualification_name	Doctor of Philosophy (PhD.)
qualification_level	Doctorate
author	Yeap, Swee Keong
author_facet	Yeap, Swee Keong
author_sort	Yeap, Swee Keong
title	Immunomodulatory Effects of Rhaphidophora Korthalsii Methanol Extract on Natural Killer Cell Activation and Cytolytic Activity
title_short	Immunomodulatory Effects of Rhaphidophora Korthalsii Methanol Extract on Natural Killer Cell Activation and Cytolytic Activity
title_full	Immunomodulatory Effects of Rhaphidophora Korthalsii Methanol Extract on Natural Killer Cell Activation and Cytolytic Activity
title_fullStr	Immunomodulatory Effects of Rhaphidophora Korthalsii Methanol Extract on Natural Killer Cell Activation and Cytolytic Activity
title_full_unstemmed	Immunomodulatory Effects of Rhaphidophora Korthalsii Methanol Extract on Natural Killer Cell Activation and Cytolytic Activity
title_sort	immunomodulatory effects of rhaphidophora korthalsii methanol extract on natural killer cell activation and cytolytic activity
granting_institution	Universiti Putra Malaysia
granting_department	Faculty Biotechnology and Biomolecular Sciences
publishDate	2010
url	http://psasir.upm.edu.my/id/eprint/9835/1/FBSB_2010_2_A.pdf
_version_	1747811005809819648

Immunomodulatory Effects of Rhaphidophora Korthalsii Methanol Extract on Natural Killer Cell Activation and Cytolytic Activity

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