Journal of Cancer Prevention

Korean Society of Cancer Prevention (대한암예방학회)
권호 표지

Immunostimulating Activity of Sarijang through Activation of MAPKs Signaling Pathway in RAW264.7 Macrophages

RAW264.7 대식세포에서 MAPKs 경로 활성을 통한 사리장의 면역활성 증가

  • Park, Hye Young (Department of Biochemistry, Dong-Eui University College of Oriental Medicine) ;
  • Jeong, Jin-Woo (Anti-Aging Research Center & Blue-Bio Industry RIC, Dong-Eui University) ;
  • Choi, Yung Hyun (Department of Biochemistry, Dong-Eui University College of Oriental Medicine) ;
  • Choi, Eun-A (Insan Bamboo Salt Inc. and Insan Oriental Medical Clinic)
  • 박혜영 (동의대학교 한의과대학 생화학교실) ;
  • 정진우 (동의대학교 항노화연구소 및 블루바이오소재개발센터) ;
  • 최영현 (동의대학교 한의과대학 생화학교실) ;
  • 최은아 ((주)인산죽염촌 및 인산한의원)
  • Published : 2012.12.31
⟨ Previous Next ⟩

Abstract

Sarijang is a bamboo salt sauce containing extracts of Rhynchosia nulubilis, Ulmus davidiana roots, Allium sativum, and has been used as nonspecific immunostimulants for cancer patients. However, its immunomodulating effects are not fully understood. In this study, the signaling mechanism of sarijang was investigated in RAW264.7 macrophages to evaluate its immunostimulating properties. We found that sarijang was capable of up-regulation of nitric oxide (NO) and tumor necrosis factor (TNF)-$\alpha$ production without affecting cell viability. Sarijang also increased the levels of mRNA and protein expression of inducible nitric oxide synthase (iNOS) suggesting that sarijang-induced expression of iNOS was liable for induction of NO production. In addition, our data indicated that sarijang-induced production of TNF-$\alpha$ was associated with the induction of mRNA expression of TNF-$\alpha$. Moreover, sarijang exhibited immuno-stimulating properties by activation of mitogen-activated protein kinases (MAPKs) such as extracellular signal-regulated kinase (ERK), p38 MAPK, and c-Jun N-terminal kinase (JNK). Based on these data, we suggeste that sarijang may potentially regulate the immune response.

Keywords

References

  1. Von Hoff DD, Layard MW, Basa P, Davis HL Jr, Von Hoff AL, Rozencweig M, Muggia FM. Risk factors for doxorubicininduced congestive heart failure. Ann Intern Med 91, 710-717, 1979. https://doi.org/10.7326/0003-4819-91-5-710
  2. Saltiel E, McGuire W. Doxorubicin (adriamycin) cardiomyopathy. West J Med 139, 332-341, 1983.
  3. Wasser SP. Medicinal mushrooms as a source of antitumor and immunomodulating polysaccharides. Appl Microbiol Biotechnol 60, 258-274, 2002. https://doi.org/10.1007/s00253-002-1076-7
  4. Kim HS, Kim JY, Kang JS, Kim HM, Kim YO, Hong IP, Lee MK, Hong JT, Kim Y, Han SB. Cordlan polysaccharide isolated from mushroom Cordyceps militaris induces dendritic cell maturation through toll-like receptor 4 signalings. Food Chem Toxicol 48, 1926-1933, 2010. https://doi.org/10.1016/j.fct.2010.04.036
  5. Klimp AH, de Vries EGE, Scherphof GL, Daemen T. A potential role of macrophage activation in the treatment of cancer. Crit Rev Oncol Hematol 44, 143-161, 2002. https://doi.org/10.1016/S1040-8428(01)00203-7
  6. Medzhitov R, Janeway C. Innate immune recognition: mechanisms and pathways. Immunol Rev 173, 89-97, 2000.
  7. Lee JS, Min KM, Cho JY, Hong EK. Study on macrophage activation and structural characteristics of purified polysaccharides from the fruiting body of Hericium erinaceus. J Microbiol Biotechnol 19, 951-959, 2009. https://doi.org/10.4014/jmb.0901.013
  8. Ross GD, Cain JA, Myones BL, Newman SL, Lachmann PJ. Specificity of membrane complement receptor type three (CR3) for beta-glucans. Complement 4, 61-H74, 1987. https://doi.org/10.1159/000463010
  9. Brown GD, Gordon S. Immune recognition: a new receptor for beta-glucans. Nature 413, 36-37, 2001.
  10. Chan GC, Chan WK, Sze DM. The effects of $\alpha$-glucan on human immune and cancer cells. J Hematol Oncol 2, 25-35, 2009. https://doi.org/10.1186/1756-8722-2-25
  11. Nielsen IL, Williamson G. Review of the factors affecting bioavailability of soy isoflavones in humans. Nutr Cancer 57, 1-10, 2007. https://doi.org/10.1080/01635580701267677
  12. Chirumbolo S. The role of quercetin, flavonols and flavones in modulating inflammatory cell function. Inflamm Allergy Drug Targets 9, 263-285, 2010. https://doi.org/10.2174/187152810793358741
  13. Ishimi Y. Dietary equol and bone metabolism in postmenopausal Japanese women and osteoporotic mice. J Nutr 140, 1373S-1376S, 2010. https://doi.org/10.3945/jn.110.124842
  14. La Ferla B, Airoldi C, Zona C, Orsato A, Cardona F, Merlo S, Sironi E, D'Orazio G, Nicotra F. Natural glycoconjugates with antitumor activity. Nat Prod Rep 28, 630-648, 2011. https://doi.org/10.1039/c0np00055h
  15. Lee Y, Park H, Ryu HS, Chun M, Kang S, Kim HS. Effects of elm bark (Ulmus davidiana var. japonica) extracts on the modulation of immunocompetence in mice. J Med Food 10, 118-125, 2007. https://doi.org/10.1089/jmf.2006.078
  16. Lee MY, Seo CS, Ha H, Jung D, Lee H, Lee NH, Lee JA, Kim JH, Lee YK, Son JK, Shin HK. Protective effects of Ulmus davidiana var. japonica against OVA-induced murine asthma model via upregulation of heme oxygenase-1. J Ethnopharmacol 130, 61-69, 2010. https://doi.org/10.1016/j.jep.2010.04.011
  17. Kim EJ, Jang MK, Yoon EH, Jung CY, Nam DW, Lee SD, Kim KS. Efficacy of pharmacopuncture using root bark of Ulmus davidiana Planch in patients with knee osteoarthritis: a double-blind randomized controlled trial. J Acupunct Meridian Stud 3, 16-23, 2010. https://doi.org/10.1016/S2005-2901(10)60003-9
  18. Choi Y, Lee MK, Lim SY, Sung SH, Kim YC. Inhibition of inducible NO synthase, cyclooxygenase-2 and interleukin-1 ${\beta}$ by torilin is mediated by mitogen-activated protein kinases in microglial BV2 cells. Br J Pharmacol 156, 933-940, 2009. https://doi.org/10.1111/j.1476-5381.2009.00022.x
  19. Resch KL, Ernst E. Garlic (Allium sativum)-a potent medicinal plant]. Fortschr Med 113, 311-315, 1995.
  20. Gorinstein S, Jastrzebski Z, Namiesnik J, Leontowicz H, Leontowicz M, Trakhtenberg S. The atherosclerotic heart disease and protecting properties of garlic: contemporary data. Mol Nutr Food Res 51, 1365-1381, 2007. https://doi.org/10.1002/mnfr.200700064
  21. Sabater-Molina M, Larque E, Torrella F, Zamora S. Dietary fructooligosaccharides and potential benefits on health. J Physiol Biochem 65, 315-328, 2009. https://doi.org/10.1007/BF03180584
  22. Gullett NP, Ruhul Amin AR, Bayraktar S, Pezzuto JM, Shin DM, Khuri FR, Aggarwal BB, Surh YJ, Kucuk O. Cancer prevention with natural compounds. Semin Oncol 37, 258-281, 2010. https://doi.org/10.1053/j.seminoncol.2010.06.014
  23. Park HY, Choi YH, Choi EA. Anti-inflammatory effects of sarijang in lipopolysaccharide-activated BV2 microglial cells. Cancer Prev Res 16, 348-357, 2011.
  24. Jin CY, Han MH, Park C, Hwang HJ, Choi EA, Choi YH. Sarijang enhances maturation of murine bone marrow-derived dendritic cells. J Life Sci 21, 1789-1794, 2011. https://doi.org/10.5352/JLS.2011.21.12.1789
  25. Murakami A, Ohigashi H. Targeting NOX, INOS and COX-2 in inflammatory cells: chemoprevention using food phytochemicals. Int J Cancer 121, 2357-2363, 2007. https://doi.org/10.1002/ijc.23161
  26. Keibel A, Singh V, Sharma MC. Inflammation, microenvironment, and the immune system in cancer progression. Curr Pharm Des 15, 1949-1955, 2009. https://doi.org/10.2174/138161209788453167
  27. Lonkar P, Dedon PC. Reactive species and DNA damage in chronic inflammation: reconciling chemical mechanisms and biological fates. Int J Cancer 128, 1999-2009, 2011. https://doi.org/10.1002/ijc.25815
  28. Keller R, Geiges M, Keist R. L-arginine-dependent reactive nitrogen intermediates as mediators of tumor cell killing by activated macrophages. Cancer Res 50, 1421-1425, 1990.
  29. Yoshimura A. Signal transduction of inflammatory cytokines and tumor development. Cancer Sci 97, 439-447, 2006. https://doi.org/10.1111/j.1349-7006.2006.00197.x
  30. Zamarron BF, Chen W. Dual roles of immune cells and their factors in cancer development and progression. Int J Biol Sci 7, 651-658, 2011. https://doi.org/10.7150/ijbs.7.651
  31. Suffys P, Beyaert R, Van Roy F, Fiers W. Involvement of a serine protease in tumornecrosis-factor-mediated cytotoxicity. Eur J Biochem 178, T257-T265, 1988. https://doi.org/10.1111/j.1432-1033.1988.tb14451.x
  32. Goossens V, Grooten J, De Vos K, Fiers W. Direct evidence for tumor necrosis factor-induced mitochondrial reactive oxygen intermediates and their involvement in cytotoxicity. Proc Natl Acad Sci USA 92, 8115-8119, 1995. https://doi.org/10.1073/pnas.92.18.8115
  33. Schorey JS, Cooper AM. Macrophage signalling upon mycobacterial infection: the MAP kinases lead the way. Cell Microbiol 5, 133-142, 2003. https://doi.org/10.1046/j.1462-5822.2003.00263.x
  34. Gaestel M, Mengel A, Bothe U, Asadullah K. Protein kinases as small molecule inhibitor targets in inflammation. Curr Med Chem 14, 2214-2234, 2007. https://doi.org/10.2174/092986707781696636
  35. Ma FY, Liu J, Nikolic-Paterson DJ. The role of stressactivated protein kinase signaling in renal pathophysiology. Braz J Med Biol Res 42, 29-37, 2009. https://doi.org/10.1590/S0100-879X2008005000049