Rhaphidophora korthalsii modulates peripheral blood natural killer cell proliferation, cytokine secretion and cytotoxicity

BMC Complementary and Alternative Medicine

Noorjahan Banu Alitheen²  Abdul Manaf Ali⁵  Boon Kee Beh⁴  Wan Yong Ho²  Abdul Rahman Omar³  Swee Keong Yeap¹ 

[1] Institute of Bioscience, University Putra Malaysia, Serdang, Selangor, Malaysia;Department of Cell and Molecular Biology, Faculty of Biotechnology and Biomolecular Sciences, University Putra Malaysia, 43400, Serdang, Selangor, Malaysia;Department of Veterinary Pathology and Microbiology, Faculty of Veterinary Medicine, University Putra Malaysia, Serdang, Selangor, Malaysia;Department of Bioprocess Technology, Faculty of Biotechnology and Biomolecular Sciences, University Putra Malaysia, 43400, Serdang, Selangor, Malaysia;Faculty of Agriculture and Biotechnology, University Sultan Zainal Abidin, Kampus Kota, Jalan Sultan Mahmud, Kuala Terengganu 20400, Malaysia

关键词: Immunomodulation;    NK cell;    Rhaphidophora korthalsii;   

Others  :  1229436
DOI  :  10.1186/1472-6882-13-145

 received in 2012-08-26, accepted in 2013-06-10,  发布年份 2013

【 摘 要 】

Background

Rhaphidophora korthalsii (Araceae) is a root-climber plant which has been widely used in Chinese traditional medicine for cancer and skin disease treatment. Previous reports have recorded its immunomodulatory effects on mice splenocyte and human peripheral blood. This study investigated the potential immunostimulatory effect of Rhaphidophora korthalsii on human PBMC enriched NK cell.

Methods

PBMC was exposed to various concentrations of R. korthalsii extract and the T and NK cell population in the control and extract treated PBMC were identified by immunophenotyping. Intracellular perforin and granzyme B expressions were detected by flow cytometry and extra-cellular Granzyme B, IFN-γ and TNF-α production in the isolated NK cells were determined by ELISA. The cytotoxicity of effector NK cell towards target K562 cell was assessed by CytoTox 96 assay.

Results

Rhaphidophora korthalsii methanol extract significantly increased PBMC NK cell population and intracellular perforin and granzyme B expressions. Moreover, the extract also enhanced the secretion of IFN-γ and TNF-α which subsequently enhanced the cytotoxicity of NK cell against the NK sensitive target K562 cell line. NK cell enriched with extract treated PBMC showed better activation than NK cell directly treated with the extract.

Conclusion

Our findings indicated a potential IL-2 free immunotherapy through direct and indirect R. korthalsii stimulation on NK cell activation.

【 授权许可】

   
2013 Yeap et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

Figure 3.

Figure 4.

Figure 5.

Figure 1.

Figure 2.

Figure 3.

Figure 4.

Figure 5.

【 参考文献 】

• [1]Wang Y, Wang W, Li N, Yu Y, Cao X: Activation of antigen-presenting cells by immunostimulatory plant DNA: a natural resource for potential adjuvant. Vaccine 2002, 20:2764-2771.
• [2]Federica C, Cristina N, Anna C, Nunziatina DT, Antoonella L, Lucia M: In vitro binding studies of methanolic extracts from different Salvia species. Pharmacologyonline Young Researchers 2006, 1:1-10.
• [3]Darien BJ, Godbee RG: Morinda citrifolia based formulations for regulating T cell immunomodulation in neonatal stock animals. In US 2009/0068204A. Edited by MCCONKIE K a. US: ; 2009.
• [4]Kumar RA, Sridevi K, Kumar NV, Nanduri S, Rajagopal S: Anticancer and immunostimulatory compounds from Andrographis paniculata. J Ethnopharmacol 2004, 92:291-295.
• [5]Kiritikar KR, Basu BD: Indian medical plant. pp. 3578–3622. Dehradum: Oriental Enterprises; 2001.
• [6]Lau TT, Ong LB, Fang TH: The antioxidant potential and immunomodulating activity of dragon plant. 2004. Retrieve 31 May, 2010 from http://www.science.edu.sg/ssc/events.jsp?artid=5705&type=17&root=268&parent=268&cat=330 webcite
• [7]Tan ML, Muhammad TST, Najimudin N, Sulaiman SF: Growth arrest and non-apoptotic programmed cell death associated with the up-regulation of c-myc mRNA expression in T-47D breast tumor cells following exposure to Epipremnum pinnatum (L.) Engl. hexane extract. J Ethnopharmacol 2005, 96:375-383.
• [8]Wong KT, Tan BKH: In vitro cytotoxicity and immunomodulating property of Rhaphidophora korthalsii. J Ethnopharmacol 1996, 52:53-57.
• [9]Yeap SK, Alitheen NB, Ali AM, Omar AR, Raha AR, Suraini AA, Muhajir AH: Effect of Rhaphidophora korthalsii methanol extract on human peripheral blood mononuclear cell proliferation and cytolytic activity toward HepG2. J Ethnopharmacol 2007, 114:406-411.
• [10]Yeap SK, Omar AR, Ali AM, Ho WY, Beh BK, Alitheen NB: Immunomodulatory effect of Rhaphidophora korthalsii on natural killer cell cytotoxicity. Evidence-Based Complementary and Alternative Medicine 2012, 2012:Aritcle ID 786487.
• [11]Yeap SK, Alitheen NBM, Ho WY, Omar AR, Ali AM, Beh BK, Yousr AHN: Immunomodulatory role of Rhaphidophora korthalsii methanol extract on human peripheral blood mononuclear cell proliferation, cytokine secretion and cytolytic activity. Journal of Medicinal Plant Research. 2011, 5:958-965.
• [12]Gobel TWF, Kaspers B, Stangassinger M: NK and T cells constitute two major, functionally distinct intestinal epithelial lymphocyte subsets in the chicken. Int Immunol 2001, 13:757-762.
• [13]Ozdemir O, Savasan S: Combinational IL-2/IL-15 induction does not further enhance IL-15-induced lymphokine-activated killer cell cytotoxicity against human leukemia/lymphoma cells. Clin Immunol 2005, 115:240-249.
• [14]Porrata LF, Inwards DJ, Lacy MQ, Markovic SN: Immunomodulation of early engrafted natural killer cells with interleukin-2 and interferon-alpha in autologous stem cell transplantation. Bone Marrow Transplant 2001, 28:673-680.
• [15]Perussia B, Ramoni C, Anegon I, Cuturi MC, Faust J, Trinchieri G: Preferential proliferation of natural killer cells among peripheral blood mononuclear cells cocultured with B lymphoblastoid cell lines. Nat Immun Cell Growth Regul 1987, 6:171-188.
• [16]Wahlberg BJ, Burholt DR, Kornblith P, Richards TJ, Bruffsky A, Herberman RB, Vujanovic NL: Measurement of NK activity by the microcytotoxicity assay (MCA): a new application for an old assay. J Immunol Methods 2001, 253:69-81.
• [17]Li Q, Nakadai A, Ishizaki M, Morimoto K, Ueda A, Krensky AM, Kawada T: Dimethyl 2,2-dichlorovinyl phosphate (DDVP) markedly decreases the expression of perforin, granzyme A and granulysin in human NK-92CI cell line. Toxicology 2005, 213:107-116.
• [18]Trapani JA, Klein JL, White PC, Dupont B: Molecular cloning of an inducible serine esterase gene from human cytotoxic lymphocytes. Proc Natl Acad Sci 1988, 85:6924-6928.
• [19]Li Q, Nakadai A, Takeda K, Kawada T: Dimethyl 2,2-dichlorovinyl phosphate (DDVP) markedly inhibits activities of natural killer cells, cytotoxic T lymphocytes and lymphokine-activated killer cells via the Fas-ligand/Fas pathway in perforin-knockout (PKO) mice. Toxicology 2004, 204:41-50.
• [20]Kim HR, Park HJ, Park J, Kim S, Kim K, Kim J: Characteristics of the killing mechanism of human natural killer cells against hepatocellular carcinoma cell lines HepG2 and Hep3B. Cancer Immunol Immunother 2004, 53:461-470.
• [21]Santarelli L, Bracci M, Mocchegiani E: In vitro and in vivo effects of mercuric chloride on thymic endocrine activity, NK and NKT cell cytotoxicity, cytokine profiles (IL-2, IFN-γ, IL-6): Role of the nitric oxide-L-arginine pathway. Int Immunopharmacol 2006, 6:376-389.
• [22]Su L, Tian H, Xu Y, Geng Y: NK activity of lymphocyte subsets and the effects of low dose radiation. Chinese Journal of Cancer Research 1998, 10:37-40.
• [23]Poli A, Michel T, Theresine M, Andres E, Hentges F, Zimmer J: CD56bright natural killer (NK) cells: an important NK cell subset. Immunology 2009, 126:458-465.
• [24]Reis E, Sousa C: Activation of dendritic cells: translating innate into adaptive immunity. Curr Opin Immunol 2004, 16:21-25.
• [25]Krishnaraj R, Bhooma T: Cytokine sensitivity of human NK cells during immunosenescence. 2. IL2-induced Interferon gamma secretion. Immunol Lett 1996, 50:59-63.
• [26]Rohner A, Langenkamp U, Siegler U, Kalberer CP, Wodnar-Filipowicz A: Differentiation-promoting drugs up-regulate NKG2D ligand expression and enhance the susceptibility of acute myeloid leukemia cells to natural killer cell-mediated lysis. Leuk Res 2007, 31:1393-1402.
• [27]Cao W, Xi X, Wang Z, Dong L, Hao Z, Cui L, Ma C, He W: Four novel ULBP splice variants are ligands for human NKG2D. Int Immunol 2008, 20:981-991.
• [28]Rushfeldt C, Sveinbjornsson B, Seljelid R, Smedsrod B: Early events of hepatic metastasis formation in mice: Role of kupffer and NK-cells in natural and interferon-γ-stimulated defense. J Surg Res 1999, 82:209-215.
• [29]Ida H, Utz PJ, Anderson P, Eguchi K: Granzyme B and natural killer (NK) cell death. Mod Rheumatol 2005, 15:315-322.