Evidence of hydrolyzed traditional Korean red ginseng by malted barley on activation of receptor interacting proteins 2 and IkappaB kinase-beta in mouse peritoneal macrophages
0
조회
0
다운로드
0
인용
0
참고문헌
키워드
초록
Red ginseng, which has a variety of biological and pharmacological activities including antioxidant, anti-inflammatory, antimutagenic and anticarcinogenic effects, has been used for thousands of years as a general tonic in traditional oriental medicine. Here, we tested the immune regulatory activities of hydrolyzed red ginseng by malted barley (HRG) on the expressions of receptor interacting proteins (Rip) 2 and IB kinase-β (IKK-β) in mouse peritoneal macrophages. We show that HRG increased the activations of Rip 2 and IKK-β for the first time. When HRG was used in combination with recombinant interferon-γ (rIFN-γ), there was a marked cooperative induction of nitric oxide (NO) production. The increased expression of inducible NO synthase from rIFN-γ plus HRG-stimulated cells was almost completely inhibited by pre-treatment with pyrrolidine dithiocarbamate (PDTC), an inhibitor of nuclear factor-B (NF-κB). In addition, the treatment of peritoneal macrophages with rIFN-γ plus HRG caused significant increases in tumor necrosis factor (TNF)-α mRNA expression and production. Because NO and TNF-α play an important role in the immune function and host defense, HRG treatment can modulate several aspects of the host defense mechanisms as a result of the stimulations of the inducible nitric oxide synthase and NF-B. In conclusion, our findings demonstrate that HRG increases the productions of NO and TNF-α from rIFN-γ-primed macrophages and suggest that Rip2/IKK-β plays a critical role in mediating these immune regulatory effects of HRG.
Abstract
Red ginseng, which has a variety of biological and pharmacological activities including antioxidant, anti-inflammatory, antimutagenic and anticarcinogenic effects, has been used for thousands of years as a general tonic in traditional oriental medicine. Here, we tested the immune regulatory activities of hydrolyzed red ginseng by malted barley (HRG) on the expressions of receptor interacting proteins (Rip) 2 and IB kinase-β (IKK-β) in mouse peritoneal macrophages. We show that HRG increased the activations of Rip 2 and IKK-β for the first time. When HRG was used in combination with recombinant interferon-γ (rIFN-γ), there was a marked cooperative induction of nitric oxide (NO) production. The increased expression of inducible NO synthase from rIFN-γ plus HRG-stimulated cells was almost completely inhibited by pre-treatment with pyrrolidine dithiocarbamate (PDTC), an inhibitor of nuclear factor-B (NF-κB). In addition, the treatment of peritoneal macrophages with rIFN-γ plus HRG caused significant increases in tumor necrosis factor (TNF)-α mRNA expression and production. Because NO and TNF-α play an important role in the immune function and host defense, HRG treatment can modulate several aspects of the host defense mechanisms as a result of the stimulations of the inducible nitric oxide synthase and NF-B. In conclusion, our findings demonstrate that HRG increases the productions of NO and TNF-α from rIFN-γ-primed macrophages and suggest that Rip2/IKK-β plays a critical role in mediating these immune regulatory effects of HRG.
참고문헌 (31)
- An HJ, "Induction of nitric oxide & tumour necrosis factor-alpha by Psoralea corylifolia", Indian J Med Res, 128, pp.752~758 (2008)
- Baldwin AS Jr, "The NF-kappa B and I kappa B proteins: new discoveries and insights", Annu Rev Immunol, 14, pp.649~683 (1996)
- Choi HS, "Red ginseng acidic polysaccharide(RGAP)in combination with IFN-gamma results in enhanced macrophage function through activation of the NF-kappaB pathway", Biosci Biotechnol Biochem, 72, pp.1817~1825 (2008)
- Chung HS, "Water extract isolated from Chelidonium majus enhances nitric oxide and tumour necrosis factor-alpha production via nuclear factor-kappaB activation in mouse peritoneal macrophages", J Pharm Pharmacol, 56, pp.129~134 (2004)
- Fontanini D, "Study of metallopeptidase isozymes from malted barley (Hordeum vulgare cv.Morex)", J Agr Food Chem, 49, pp.4903~4911 (2001)
- Gantt KR, "Oxidative responses of human and murine macrophages during phagocytosis of Leishmania chagasi", J Immunol, 167, pp.893~901 (2001)
- Ghosh S, "NF-kB and Rel proteins : evolutionarily conserved mediators of immune responses", Ann Rev immunol, 16, pp.225~260 (1998)
- Gorjanovic S, "Isolation and characterization of highly liganded protein from brewer's barley grain", Biosci Biotech Bioch, 66, pp.1940~1944 (2002)
- Dae-Chul Ha, "Change in Ginsenosides and Maltol in Dried Raw Ginseng during Extrusion Process", Food Science and Biotechnology, 14(3), pp.363~367 (2005), 한국식품과학회
- Inohara N, "RICK, a novel protein kinase containing a caspase recruitment domain, interacts with CLARP and regulates CD95-mediated apoptosis", J Biol Chem, 273, pp.12296~12300 (1998)
- Inohara N, "An induced proximity model for NF-kappa B activation in the Nod1", RICK and RIP signaling pathways, 2000, pp.275, 27823~27831
- Jeong HJ, "Role of Ca(2+)on TNF-alpha and IL-6 secretion from RBL-2H3 mast cells", Cell Signal, 14, pp.633~639 (2002)
- Joo SS, "Hematopietic effect of ginsenoside Rg3 in ICR mouse primary cultures and its application to a biological response modifier", Fitoterapia, 75, pp.337~341 (2004)
- Karin M, "The beginning of the end : IkappaB kinase(IKK)and NF-kappaB activation", J Biol Chem, 274, pp.27339~27342 (1999)
- Kim WY, "Steaming of ginseng at high temperature enhances biological activity", J Nat Prod, 63, pp.1702~1704 (2000)
- Kobayashi K, "RICK", Rip2, Nature, pp.2002, 416[DOI]
- Lee TK, "Radioprotective potential of ginseng", Mutagenesis, 20, pp.237~239 (2005)
- 남기열, "홍삼과 백삼의 비교 고찰", Journal of Ginseng Research, 29(1), pp.1~18 (2005), 고려인삼학회
- Nathan C, "Nitric oxide as a secretory product of mammalian cells", Faseb J, 6, pp.3051~3064 (1992)
- Park JD, "Recent studies on the chemical constituents of Korean ginseng (Panax ginseng C.A.Meyer)", Korean J Ginseng Sci, 20, pp.389~415 (1996)
- Park JH, "Anxiolytic-like effects of ginseng in the elevated plus-maze model : comparison of red ginseng and sun ginseng", Prog Neuro-Psychoph, 29, pp.895~900 (2005)
- Rhim H, "Ginseng and ginsenoside Rg3, a newly identified active ingredient of ginseng, modulate Ca2+ channel currents in rat sensory neurons", Eur J Pharmcol, 436, pp.151~158 (2002)
- Scherer DC, "Signal-induced degradation of I kappa B alpha requires site-specific ubiquitination", Proc Natl Acad Sci USA, 92, pp.11259~11263 (1995)
- Shin HM, "Inhibitory action of novel aromatic diamine compound on lipopolysaccharide-induced nuclear translocation of NF-kappaB without affecting IkappaB degradation", FEBS Lett, 571, pp.50~54 (2004)
- Stewart ML, "Molecular weight of guar gum affects short-chain fatty acid profile in model intestinal fermentation", Mol Nutr Food Res, 50, pp.971~976 (2006)
- Takagu T, "Studies on insulin-like substances in Korean red ginseng", Planta Med, 56, pp.27~30 (1990)
- Tao H, "Effect of angiogenesis inhibitor Rg3 on the growth and metastasis of gastric cancer in SCID mice", Zhounghua Wai Ke Za Zhi, 40, pp.606~608 (2002)
- Thanos D, "NF-kB : a lesson in family values", Cell, 80, pp.529~532 (1995)
- Tian JW, "Neuroprotective effect of 20(S)-ginsenoside Rg3 on cerebral ischemia in rats", Neurosci Lett, 374, pp.92~97 (2005)
- Yun TK, "Experimental and epidemiological evidence on non-organ specific cancer preventive effect of Korean ginseng and identification of active compounds", Mutat Res, 523, pp.63~74 (2003)
- Yun TK, "Anticarcinogenic effect of Panax ginseng C.A. Meyer and identification of active compounds", J Korean Med Sci, 16, pp.6~18 (2001)