DOI QR코드

DOI QR Code

Immunostimulatory Effects of Cordyceps militaris on Macrophages through the Enhanced Production of Cytokines via the Activation of NF-${\kappa}B$

  • Received : 2010.03.01
  • Accepted : 2010.03.31
  • Published : 2010.04.30

Abstract

Background: Cordyceps militaris has been used in traditional medicine to treat numerous diseases and has been reported to possess both antitumor and immunomodulatory activities in vitro and in vivo. However, the pharmacological and biochemical mechanisms of Cordyceps militaris extract (CME) on macrophages have not been clearly elucidated. In the present study, we examined how CME induces the production of proinflammatory cytokines, transcription factor, and the expression of co-stimulatory molecules. Methods: We confirmed the mRNA and protein levels of proinflammatory cytokines through RT-PCR and western blot analysis, followed by a FACS analysis for surface molecules. Results: CME dose dependently increased the production of NO and proinflammatory cytokines such as IL-$1{\beta}$, IL-6, TNF-${\alpha}$, and $PGE_2$, and it induced the protein levels of iNOS, COX-2, and proinflammatory cytokines in a concentrationdependent manner, as determined by western blot and RT-PCR analysis, respectively. The expression of co-stimulatory molecules such as ICAM-1, B7-1, and B7-2 was also enhanced by CME. Furthermore, the activation of the nuclear transcription factor, NF-${\kappa}B$ in macrophages was stimulated by CME. Conclusion: Based on these observations, CME increased proinflammatory cytokines through the activation of NF-${\kappa}B$, further suggesting that CME may prove useful as an immune-enhancing agent in the treatment of immunological disease.

Keywords

References

  1. Gai G, Jin S, Wang B, Li Y, Li C: The efficacy of Cordyceps militaris capsules in treatment of chronic bronchitis in comparison with Jinshuibao capsules. Chin J New Drugs 13; 169-171, 2004
  2. Choi SB, Park CH, Choi MK, Jun DW, Park S: Improvement of insulin resistance and insulin secretion by water extracts of cordyceps militaris, phellinus linteus, and paecilomyces tenuipes in 90% pancreatectomized rats. Biosci Biotechnol Biochem 68;2257-2264, 2004 https://doi.org/10.1271/bbb.68.2257
  3. Yun Y, Han S, Lee S, Ko S, Lee C, Ha N, Kim K: Anti-diabetic effects of CCCA, CMESS, and cordycepin from Cordyceps militaris and the immune responses in streptozotocin- induced diabetic mice. Nat Prod Sci 9;291-298, 2003
  4. Yu R, Wang L, Zhang H, Zhou C, Zhao Y: Isolation, purification and identification of polysaccharides from cultured Cordyceps militaris. Fitoterapia 75;662-666, 2004 https://doi.org/10.1016/j.fitote.2004.06.010
  5. Cho MA, Lee DS, Kim MJ, Sung JM, Ham SS: Antimutagenicity and cytotoxicity of cordycepin isolated from Cordyceps rnilitaris. Food Sci Biotechnol 12;472-475, 2003
  6. Won SY, Park EH: Anti-inflammatory and related pharmacological activities of cultured mycelia and fruiting bodies of Cordyceps militaris. J Ethnopharmacol 96;555-561, 2005 https://doi.org/10.1016/j.jep.2004.10.009
  7. Chen C, Luo S, Sun YJ, Zhang CK: Study on antioxidant activity of three Cordyceps sp. Chin J Biochem Pharm 25; 212-214, 2004
  8. Ross JA, Auger MJ, Burke B, Lewis CE. The biology of the macrophage. In: Burke B, Lewis CE, eds. The macrophage. 2nd ed. Oxford, UK: Oxford Medical Publications; p1-72, 2002
  9. Kinne RW, Brauer R, Stuhlmuller B, Palombo-Kinne E, Burmester GR: Macrophages in rheumatoid arthritis. Arthritis Res 2;189-202, 2000 https://doi.org/10.1186/ar86
  10. Nathan C: Inducible nitric oxide synthase: what difference does it make? J Clin Invest 100;2417-2423, 1997 https://doi.org/10.1172/JCI119782
  11. Bogdan C: Nitric oxide and the immune response. Nat Immunol 2;907-916, 2001
  12. Vila-del Sol V, Fresno M: Involvement of TNF and NF-kappa B in the transcriptional control of cyclooxygenase-2 expression by IFN-gamma in macrophages. J Immunol 174; 2825-2833, 2005
  13. Isomaki P, Punnonen J: Pro- and anti-inflammatory cytokines in rheumatoid arthritis. Ann Med 29;499-507, 1997 https://doi.org/10.3109/07853899709007474
  14. Libby P, Ridker PM, Maseri A: Inflammation and atherosclerosis. Circulation 105;1135-1143, 2002 https://doi.org/10.1161/hc0902.104353
  15. Tilg H, Wilmer A, Vogel W, Herold M, Nolchen B, Judmaier G, Huber C: Serum levels of cytokines in chronic liver diseases. Gastroenterology 103;264-274, 1992 https://doi.org/10.1016/0016-5085(92)91122-K
  16. Coker RK, Laurent GJ: Pulmonary fibrosis: cytokines in the balance. Eur Respir J 11;1218-1221, 1998 https://doi.org/10.1183/09031936.98.11061218
  17. Lawrence T, Gilroy DW, Colville-Nash PR, Willoughby DA: Possible new role for NF-kappaB in the resolution of inflammation. Nat Med 7;1291-1297, 2001 https://doi.org/10.1038/nm1201-1291
  18. Riehemann K, Behnke B, Schulze-Osthoff K: Plant extracts from stinging nettle (Urtica dioica), an antirheumatic remedy, inhibit the proinflammatory transcription factor NFkappaB. FEBS Lett 442;89-94, 1999 https://doi.org/10.1016/S0014-5793(98)01622-6
  19. Renard P, Raes M: The proinflammatory transcription factor NFkappaB: a potential target for novel therapeutical strategies. Cell Biol Toxicol 15;341-344, 1999 https://doi.org/10.1023/A:1007652414175
  20. Makarov SS: NF-kappaB as a therapeutic target in chronic inflammation: recent advances. Mol Med Today 6;441-448, 2000 https://doi.org/10.1016/S1357-4310(00)01814-1
  21. Stuehr DJ, Nathan CF: Nitric oxide. A macrophage product responsible for cytostasis and respiratory inhibition in tumor target cells. J Exp Med 169;1543-1555, 1989 https://doi.org/10.1084/jem.169.5.1543
  22. Majumder N, Dey R, Mathur RK, Datta S, Maitra M, Ghosh S, Saha B, Majumdar S: An unusual pro-inflammatory role of interleukin-10 induced by arabinosylated lipoarabinomannan in murine peritoneal macrophages. Glycoconj J 23; 675-686, 2006 https://doi.org/10.1007/s10719-006-9017-9
  23. MacMicking J, Xie QW, Nathan C: Nitric oxide and macrophage function. Annu Rev Immunol 15;323-350, 1997 https://doi.org/10.1146/annurev.immunol.15.1.323
  24. Underhill DM, Ozinsky A: Phagocytosis of microbes: complexity in action. Annu Rev Immunol 20;825-852, 2002 https://doi.org/10.1146/annurev.immunol.20.103001.114744
  25. Li J, Billiar TR, Talanian RV, Kim YM: Nitric oxide reversibly inhibits seven members of the caspase family via S-nitrosylation. Biochem Biophys Res Commun 240;419-424, 1997 https://doi.org/10.1006/bbrc.1997.7672
  26. Kolb H, Kolb-Bachofen V: Nitric oxide in autoimmune disease: cytotoxic or regulatory mediator? Immunol Today 19;556-561, 1998 https://doi.org/10.1016/S0167-5699(98)01366-8
  27. Paterson RR: Cordyceps: a traditional Chinese medicine and another fungal therapeutic biofactory? Phytochemistry 69;1469-1495, 2008 https://doi.org/10.1016/j.phytochem.2008.01.027
  28. Ahmad N, Chen LC, Gordon MA, Laskin JD, Laskin DL: Regulation of cyclooxygenase-2 by nitric oxide in activated hepatic macrophages during acute endotoxemia. J Leukoc Biol 71;1005-1011, 2002
  29. Seibert K, Zhang Y, Leahy K, Hauser S, Masferrer J, Perkins W, Lee L, Isakson P: Pharmacological and biochemical demonstration of the role of cyclooxygenase 2 in inflammation and pain. Proc Natl Acad Sci USA 91;12013-12017, 1994 https://doi.org/10.1073/pnas.91.25.12013
  30. Dazzi F, D'Andrea E, Biasi G, De Silvestro G, Gaidano G, Schena M, Tison T, Vianello F, Girolami A, Caligaris-Cappio F: Failure of B cells of chronic lymphocytic leukemia in presenting soluble and alloantigens. Clin Immunol Immunopathol 75;26-32, 1995 https://doi.org/10.1006/clin.1995.1048
  31. Deeths MJ, Mescher MF: ICAM-1 and B7-1 provide similar but distinct costimulation for CD8+ T cells, while CD4+ T cells are poorly costimulated by ICAM-1. Eur J Immunol 29;45-53, 1999 https://doi.org/10.1002/(SICI)1521-4141(199901)29:01<45::AID-IMMU45>3.0.CO;2-I

Cited by

  1. Immunostimulating activity of the polysaccharides isolated from Cordyceps militaris vol.11, pp.9, 2010, https://doi.org/10.1016/j.intimp.2011.04.001
  2. H2 inhibits TNF-α-induced lectin-like oxidized LDL receptor-1 expression by inhibiting nuclear factor κB activation in endothelial cells vol.33, pp.9, 2010, https://doi.org/10.1007/s10529-011-0630-8
  3. Suppression of endothelial cell adhesion by XJP-1, a new phenolic compound derived from banana peel vol.57, pp.2, 2012, https://doi.org/10.1016/j.vph.2012.05.006
  4. The Antiviral Effect of High-Molecular Weight Poly-Gamma-Glutamate against Newcastle Disease Virus on Murine Macrophage Cells vol.2014, pp.None, 2010, https://doi.org/10.1155/2014/301386
  5. Nutrigenomic Study on Immunomodulatory Function of &lt;i&gt;Cordyceps&lt;/i&gt; Mycelium Extract (&lt;i&gt;Paecilomyces hepiali&lt;/i&gt;) in Mitomycin C–Treated vol.5, pp.22, 2010, https://doi.org/10.4236/fns.2014.522235
  6. Mechanisms Underlying the Antifatigue Effects of the Mycelium Extract of &lt;i&gt;Cordyceps&lt;/i&gt; (&lt;i&gt;Paecilomyces hepiali&lt;/i&gt;, CBG-CS-2) in Mice in the vol.6, pp.2, 2010, https://doi.org/10.4236/fns.2015.62029
  7. Epimedium koreanum Nakai Displays Broad Spectrum of Antiviral Activity in Vitro and in Vivo by Inducing Cellular Antiviral State vol.7, pp.1, 2015, https://doi.org/10.3390/v7010352
  8. 밀리타리스 동충하초(Cordyceps militaris)의 인플루엔자백신 적응면역에 미치는 영향 vol.59, pp.1, 2015, https://doi.org/10.17480/psk.2015.59.1.1
  9. Anti-inflammatory effects of Cordyceps mycelium ( Paecilomyces hepiali , CBG-CS-2) in Raw264.7 murine macrophages vol.15, pp.1, 2010, https://doi.org/10.1007/s13596-014-0173-3
  10. Antiviral Effects of Novel Herbal Medicine KIOM-C, on Diverse Viruses vol.10, pp.5, 2010, https://doi.org/10.1371/journal.pone.0125357
  11. A novel protein from edible fungi Cordyceps militaris that induces apoptosis vol.26, pp.1, 2018, https://doi.org/10.1016/j.jfda.2016.10.013
  12. Effect of Cordyceps militaris Hot Water Extract on Immunomodulation-associated Gene Expression in Broilers, Gallus gallus vol.56, pp.2, 2010, https://doi.org/10.2141/jpsa.0180067
  13. Medicinal importance of mushroom mycelium: Mechanisms and applications vol.56, pp.None, 2010, https://doi.org/10.1016/j.jff.2019.03.016
  14. Study on the effect of regulation of Cordyceps militaris polypeptide on the immune function of mice based on a transcription factor regulatory network vol.11, pp.7, 2010, https://doi.org/10.1039/d0fo01043j
  15. Effect of Spent Mushroom ( Cordyceps militaris ) on Growth Performance, Immunity, and Intestinal Microflora in Weaning Pigs vol.10, pp.12, 2010, https://doi.org/10.3390/ani10122360
  16. Research progress on Cordyceps militaris polysaccharides vol.45, pp.None, 2010, https://doi.org/10.1016/j.fbio.2021.101503