대한한방부인과학회지 (The Journal of Korean Obstetrics and Gynecology)

  • 제26권2호
  • /
  • Pages.17-32
  • /
  • 2013
  • /
  • 1229-4292(pISSN)
  • /
  • 2508-3619(eISSN)
대한한방부인과학회 (The Society of Korean Medicine Obstetrics and Gynecology)
권호 표지
DOI QR코드

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금은화의 type I interferon 억제효과 및 기전에 관한 연구

A Study on the Inhibitory Effect and Mechanism of Lonicera Japonica on Type I Interferon

  • 강용구 (원광대학교 한의과대학 한방부인과학 교실) ;
  • 유익한 (원광대학교 한의과대학 한방부인과학 교실) ;
  • 김송백 (원광대학교 한의과대학 한방부인과학 교실) ;
  • 최창민 (원광대학교 한의과대학 한방부인과학 교실) ;
  • 서윤정 (원광대학교 한의과대학 한방부인과학 교실) ;
  • 조한백 (원광대학교 한의과대학 한방부인과학 교실)
  • Kang, Yong-Goo (Dept. of Oriental Obstetrics & Gynecology, College of Oriental Medicine, Won-Kwang University) ;
  • Ryu, Ik-Han (Dept. of Oriental Obstetrics & Gynecology, College of Oriental Medicine, Won-Kwang University) ;
  • Kim, Song-Baek (Dept. of Oriental Obstetrics & Gynecology, College of Oriental Medicine, Won-Kwang University) ;
  • Choi, Chang-Min (Dept. of Oriental Obstetrics & Gynecology, College of Oriental Medicine, Won-Kwang University) ;
  • Seo, Yun-Jung (Dept. of Oriental Obstetrics & Gynecology, College of Oriental Medicine, Won-Kwang University) ;
  • Cho, Han-Baek (Dept. of Oriental Obstetrics & Gynecology, College of Oriental Medicine, Won-Kwang University)
  • 투고 : 2013.04.24
  • 심사 : 2013.05.09
  • 발행 : 2013.05.31
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초록

Objectives: The purpose of this study was to investigate whether Lonicera japonica(LJ) could inhibit LPS-induced type I IFN production. Methods: To evaluate inhibitory effect of LJ on type I IFN, we examined type I IFN, IRF-1, 7 and IL-10 production on LPS-induced macrophages using real time RT-PCR. Next, we observed the interaction of type I IFN, IRF-1, 7 and IL-10 using IL-10 neutralizing antibody. Finally we examined the activation of STAT-1, 3 using western blot. Results: LJ inhibited Type I IFN expression of mRNA and increased IL-10 expression of mRNA. Also LJ inhibited the level of IRF-1, 7 mRNA and the nuclear translocation of IRF-3. Further more, LJ reduced the activation of STAT-1, 3 which are involved in continuous secretion of immune cytokines. Blockade of IL-10 action caused a significant reduction of type I IFN and IRF-1, 7 than LPS-induced LJ pretreatment. Conclusions: LJ inhibits LPS-induced production of type I IFN by IL-10. This study may provide a clinical basis for anti-inflammatory properties of LJ.

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참고문헌

  1. Abul K, Abbas AK. Cellular and Molecular Immunology. 6th edition. philadelphia:Saunders Elsevier. 2006 :75-97.
  2. 대한병리학회. 병리학. 서울:고문사. 1997 :65-66.
  3. Guha M, Mackman N. LPS induction of gene expression in human monocytes. Cellular Signal. 2001;13:85-94. https://doi.org/10.1016/S0898-6568(00)00149-2
  4. Kubes P, Mccafferty DM. Nitric oxide and intestinal inflammation. American J Medicine. 2000;109:150-158. https://doi.org/10.1016/S0002-9343(00)00480-0
  5. Rietschel ET, et al. Bacterial endotoxin: molecular relationships of structure to activity and function. FASEB J. 1994; 8(2):217-225.
  6. Galdiero F, et al. Release of cytokines induced by Salmonella typhimurium porins. Infect Immun. 1993;61(1):155-161.
  7. Platanias LC, Fish EN. Signaling pathways activated by interferons. Exp Hematol. 1999;27:1583-1592. https://doi.org/10.1016/S0301-472X(99)00109-5
  8. Sen GC. Viruses and interferons. Annu Rev Microbiol. 2001;55:255-281. https://doi.org/10.1146/annurev.micro.55.1.255
  9. Biron CA. Interferons alpha and beta as immune regulators - a new look. Immunity. 2001;14(6):661-664. https://doi.org/10.1016/S1074-7613(01)00154-6
  10. Chawla-Sarkar M, et al. Apoptosis and interferons: role of interferonstimulated genes as mediators of apoptosis. Apoptosis. 2003;8:237-249. https://doi.org/10.1023/A:1023668705040
  11. Pestka S, et al. Interferons, interferon -like cytokines, and their receptors. Immunol Rev. 2004;202:8-32. https://doi.org/10.1111/j.0105-2896.2004.00204.x
  12. Honda K, et al. Type I Interferon Gene Induction by the Interferon Regulatory Factor Family of Transcription Factors. Immunity. 2006;25:349-360. https://doi.org/10.1016/j.immuni.2006.08.009
  13. Bogdan C. The function of type I Interferons in antimicrobial immunity. Curr Opin Immunol. 2000;12(4):419-424. https://doi.org/10.1016/S0952-7915(00)00111-4
  14. Taniguchi T, et al. IRF Family of transcription factors as regulators of host defense. Annu Rev Immunol. 2001;19:623-655. https://doi.org/10.1146/annurev.immunol.19.1.623
  15. Colonna M. TLR pathways and IFN -regulatory factors: To each its own. Eur J Immunol. 2007;37:306-309. https://doi.org/10.1002/eji.200637009
  16. Baccala R, et al. TLR-dependent and TLR-independent pathways of type I interferon induced in systemic autoimmunity. Nature Med. 2007;13(5) :543-551. https://doi.org/10.1038/nm1590
  17. Karaghiosoff M, et al. Central role for type I Interferons and Tyk2 in lipopolysaccharide-induced endotoxin shock. Nat Immunol. 2003;4(5):471-477. https://doi.org/10.1038/ni910
  18. Servera M, Fitzgerald KA. TLRmediated activation of type I IFN during antiviral responses. Current topics in microbiology and immunology. 2007;316:167-192.
  19. Marie I, et al. Differential viral induction of distinct interferon-alpha genes by positive feedback through interferon regulatory factor-7. EMBO J. 1998; 17(22):6660-6669. https://doi.org/10.1093/emboj/17.22.6660
  20. Sato M, et al. Distinct and essential roles of transcription factors IRF-3 and IRF-7 in response to viruses for IFN-alpha/beta gene induction. Immunity. 2000;13(4):539-548. https://doi.org/10.1016/S1074-7613(00)00053-4
  21. Cabuk M, et al. Arthritis induced by interferon-alpha therapy in a patient with essential thrombocythemia. Leukmia and Lymphoma. 2003;44(2):377-378. https://doi.org/10.1080/1042819021000029948
  22. Nieworld TB, Gibofsky A. Concomitant interferon-alpha therapy and tumor necrosis factor alpha inhibition for rheumatoid arthritis and hepatitis C. Arthritis Rheum. 2006;54:2335-2337. https://doi.org/10.1002/art.21949
  23. Banchereau J, Pascual V. Type Ⅰ interferon in systemic lupus erythematosus and other autoimmune disease. Immunity. 2006;25:383-392. https://doi.org/10.1016/j.immuni.2006.08.010
  24. Moore KW, et al. Interleukin-10 and the interleukin-10 and the interleukin-10 recepter. Annual review of immunology. 2001;19:683-765. https://doi.org/10.1146/annurev.immunol.19.1.683
  25. Mege JL, et al. The two faces of interleukin 10 in human infectious diseases. The Lancet infectious diseases. 2006;6:557-569. https://doi.org/10.1016/S1473-3099(06)70577-1
  26. 전국한의과대학본초학교수 공편. 본초학. 서울:영림사. 2004:198-199.
  27. 김동현 등. 한방약리학. 서울:신일상사. 2006:133-135.
  28. 이상철. LPS 유도 생쥐 관절염에서 금은화의 MIF 활성 조절이 COX-2 와 MMP-9 생성 억제에 미치는 영향. 동국대학교 대학원 석사학위논문집. 2009.
  29. 채기원. 금은화의 항염작용과 파골세포 형성 억제효과. 경희대학교 대학원 박사학위논문집. 2008.
  30. 윤용갑 등. 금은화 수용성 추출물의 LPS 유도 염증매개물 억제 효과. 대한본초학회지. 2007;22(3):117-125.
  31. Kang OH, et al. Inhibition of trypsin -induced mast cell activation by water fraction of flowers of Lonicera japonica. Archives of pharmacal research. 2004;27(11):1141-1146. https://doi.org/10.1007/BF02975120
  32. 배지현 등. 식중독 유발세균의 증식에 미치는 금은화 추출물의 항균효과. 한국식품과학회지. 2005;37(4):642-647.
  33. 박희수. 금은화 약침의 항암효과에 관한 연구. 대한침구학회지. 2005;22(5) :91-97.
  34. 한재섭, 박희수. 금은화약침의 항암 및 면역반응에 관한 실험적 연구. 대한침구학회지. 2006;23(4):205-218.
  35. 이동언. 金銀花 및 金銀花全草가 Raw 264.7 cell에서 LPS로 유도된 NO의 생성, iNOS, COX-2 및 cytokine에 미치는 영향. 대구한의대학교 대학원 박사학위논문집. 2005.
  36. 김진호. 금은화 물 추출물이 Cerulein 으로 誘發된 白鼠의 급성 췌장염에 미치는 영향. 동신대학교 대학원 박사학위논문집. 2009.
  37. 이창건 등. 금은화가 LPS로 유발된 급성 폐 손상에 미치는 영향. 대한예방한의학회지. 2011;15(4):49-69.
  38. 윤경진, 이은용. 금은화 추출액이 RAW 264.7 Macrophage에서의 NO와 PGE2 생성에 미치는 영향. 대한침구학회지. 2012;29(1):67-74.
  39. 서윤정. 오미소독음의 항염효과 및 기전에 관한 실험적 연구. 대한한방부인과학회지. 2008;21(1):39-54.
  40. 염병수, 김영판. 방제의 체계적 구성을 위한 임상배합본초학. 서울:영림사. 1994:230-231.
  41. 김형균 등. 한약의 약리. 서울:고려의학. 2000:335-336.
  42. Han DS, et al. Development of anticancer agents from korean medical plants. part 6, cytoxid activity of the ethyl acetate soluble fraction of Lonicera Flos against human oral epitheloid carcinoma cells. Korean J Pharmacogn. 1998;29(1):22-27.
  43. Son KH, et al. Flavonoids from aerial parts of Lonicera japonica. Arch Pharmacol Res. 1992;15:365-370. https://doi.org/10.1007/BF02974114
  44. Lee SJ, et al. Anti-inflammatory activity of the major constituents of Lonicera japonica. Arch Pharm Res. 1995;18(2):133-135. https://doi.org/10.1007/BF02979147
  45. 동의보감국역위원회. 국역증보동의보감. 서울:남산당. 1995:508, 537, 538, 540.
  46. 김상찬 등. 방제학. 서울:영림사. 1999 :83-84.
  47. Matsuda H, et al. Structural reqirements of flavonoid for nitric oxide production inhibitory activity and mechanism of action. Bioorganic Med Chem. 2003; 11:1995-2000. https://doi.org/10.1016/S0968-0896(03)00067-1
  48. Calixto JB, et al. Anti-inflammatory compounds of plant origin. Part II. modulation of pro-inflammatory cytokines, chemokines and adhesion molecules. Planta Med. 2004;70(2) :93-103. https://doi.org/10.1055/s-2004-815483
  49. Aderem A, Ulevitch RJ. Toll-like receptors in the induction of the innate immune response. Nature. 2000;406(6797):782-787. https://doi.org/10.1038/35021228
  50. Sadler AJ, Williams BR. Interferon -inducible antiviral effectors. Nat Rev Immunol. 2008;8:559-568. https://doi.org/10.1038/nri2314
  51. Mamane Y, et al. Interferon regulatory factors: the next generation. Gene. 1999;237:1-14. https://doi.org/10.1016/S0378-1119(99)00262-0
  52. Takaoka A, et al. Integral role of IRF-5 in the gene induction programme activated by Toll-like receptors. Nature 2005;434:43-49.
  53. Miyamoto M, et al. Regulated expression of a gene encoding a nuclear factor, IRF-1, that specifically binds to IFN-beta gene regulatory elements. Cell. 1988;54:903-913. https://doi.org/10.1016/S0092-8674(88)91307-4
  54. Barnes BJ, et al. Virus-specific activation of novel interferon regulatory factor, IRF-5, result in the induction of distinct interferon alpha genes. J Biol Chem. 2001;276(26):23382-23390. https://doi.org/10.1074/jbc.M101216200
  55. Barnes BJ, et al. Virus-induced heterodimer formation between IRF-5 and IRF-7 modulates assembly of the IFN enhanceosome in vivo and transcriptional activity of IFN-$\alpha$ genes. J Biol Chem. 2003;278:16630-16641. https://doi.org/10.1074/jbc.M212609200
  56. Servant MJ, et al. Overlapping and distinct mechanisms regulating IRF-3 and IRF-7 function. J Interferon Cytokine Res. 2002;22:49-58. https://doi.org/10.1089/107999002753452656
  57. Fiorentino DF, et al. Two type of mouse helper T cell. Ⅳ. Th2 clones secrete a factor that inhibits cytokine production by Th1 clones. J Exp Med. 1989;170:2081-2095. https://doi.org/10.1084/jem.170.6.2081
  58. Fiorentino DF, et al. IL-10 acts on the antigen-presenting cell to inhibit cytokine production by Th1 cells. J Immunol. 1991;146:3444-3451.
  59. Berkaman, et al. Inhibition of induced expression of macrophage inflammatory protein-1a in human blood monocytes and alveolar macrophages by interleukin-10. J Immunol. 1995;155:4412-4418.
  60. John M, et al. Expression and release of interleukin-8 by human airway smooth muscle cells: inhibition by Th2 cytokines and corticosteroids. Am J Respir Cell Mol Biol J. 1998;18(1):84-90. https://doi.org/10.1165/ajrcmb.18.1.2813
  61. Cunha FQ, et al. Interleukin-10 (IL-10) inhibits the induction of nitric oxide synthase by interferon-gamma in murine macrophages. Biochem Biophys Res Commun. 1992;182:1155-1159. https://doi.org/10.1016/0006-291X(92)91852-H
  62. De Waal Malefty R, et al. Interleukin (IL-10) and viral IL-10 strongly reduced antigen-specific human T cell proliferation by diminishing the antigen-presenting capacity of monocytes via downregulation of class Ⅱ major histocompatibility complex expression. J Exp Med. 1991;174(4):915-924. https://doi.org/10.1084/jem.174.4.915
  63. 정원석 등. 플라보노이드 루테올린의 lipopolysaccharide로 유도한 type Ⅰ interferon 억제효과. 동의생리병리학회지. 2009;23(5):986-992.
  64. Schindler C, Darnell JE Jr. Transcriptional responses to polypeptide ligands: the JAK-STAT pathway. Annu Rev Biochem. 1995;64:621-651. https://doi.org/10.1146/annurev.bi.64.070195.003201
  65. Darnell JE Jr. STATs and gene regulation. Science. 1997;277:1630-1635. https://doi.org/10.1126/science.277.5332.1630
  66. Darnell JE Jr, et al. JAK-STAT Pathways and Transcriptional Activation in Response to IFNs and Other Extracellular Signaling Proteins. Science. 1994;5164:1415-1421.
  67. Leonard WJ. Stats and cytokine specificity. Nature Med. 1996;2:968-969. https://doi.org/10.1038/nm0996-968
  68. Leonard WJ, O'Shea JJ. Jaks and STATs: Biological implications. Annu Rev Immunol. 1998;16:293-322. https://doi.org/10.1146/annurev.immunol.16.1.293
  69. Zhong Z, et al. Stat3: a STAT family member activated by tyrosin phosphorylation in response to epidermal growth factor and interleukin-6. Science. 1994;264:95-98. https://doi.org/10.1126/science.8140422

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