THE GROWTH FACTORS EXPRESSION OF CYCLOSPORINE INDUCED GINGIVAL OVERGROWTH

Cyclosporine에 의한 치은증식에서 성장인자들의 발현연구

  • Kim, Young-Jae (Div. of Oral & Maxillofacial Surgery, Dept. of Dentstry, College of Medicine Hanyang University) ;
  • Shim, Kwang-Sup (Div. of Oral & Maxillofacial Surgery, Dept. of Dentstry, College of Medicine Hanyang University) ;
  • Hwang, Kyung-Gyun (Div. of Oral & Maxillofacial Surgery, Dept. of Dentstry, College of Medicine Hanyang University) ;
  • Oh, Young (Div. of Oral & Maxillofacial Surgery, Dept. of Dentstry, College of Medicine Hanyang University) ;
  • Paik, Seung-Sam (Department of Pathology, College of Medicine Hanyang University)
  • 김용재 (한양대학교 의과대학 치과학교실 구강악안면외과) ;
  • 황경균 (한양대학교 의과대학 치과학교실 구강악안면외과) ;
  • 오영 (한양대학교 의과대학 치과학교실 구강악안면외과) ;
  • 백승삼 (한양대학교 의과대학 병리학교실) ;
  • 심광섭 (한양대학교 의과대학 치과학교실 구강악안면외과)
  • Published : 2005.09.30

Abstract

Cyclosporine A(CsA) is a powerful immunossuppresive agent used to prevent graft rejection of organ and treat autoimmune disease. One of the major side effects associated with CsA treatment is the development of gingival overgrowth. The purpose of this study was to evaluate the expression and association of the several growth factors in gingival overgrowth induced CsA using by immunohistochemical technique. Normal tissues as control were obtained from healthy normal gingivae and overgrowth gingival tissues as experiments were obtained from the patients taken the CsA. The expressions of the MMP-1, TIMP-1, TGF$\beta$-1, p21, p53, PCNA were evaluated by immunohistochemical technique. The more overgrowth was detected at the epithelial and connective tissue area in experimental group. The MMP-1, TGF$\beta$-1, p21, p53, PCNA expressions were significantly increased in experimental group. The TIMP-1 expressions was not significantly increased in experimental group. We could conclude that the gingival overgrowth induced CsA was related with the collagen matabolism in connective tissue and also the production of the growth factor from epithelial tissue.

Keywords

References

  1. Boltchi FE, Rees TD, Iacopino AM : Cyclosporine Ainduced gingival overgrowth: a comprehensive review. Quintessence Int 30 : 775, 1999
  2. Kantarci A, Cebeci I, Tuncer O et al : Clinical effects of periodontal therapy on the severrity of cyclosporin Ainduced gingival hyperplasia. J Periodontol 70 : 587, 1999 https://doi.org/10.1902/jop.1999.70.6.587
  3. Tipton DA, Fry HR, Dabbous MK : Altered collagen metabolism in nifedipine-induced gingival overgrowth. J Periodontal Res 29 : 401, 1994 https://doi.org/10.1111/j.1600-0765.1994.tb01241.x
  4. Brown RS, Beaver WT, Bottomley WK : On the mechanism of drug-induced gingival hyperplasia. J Oral Pathol Med 20 : 201, 1991 https://doi.org/10.1111/j.1600-0714.1991.tb00419.x
  5. Seymour RA, Thomason JM, Ellis JS : The pathogenesis of drug-induced gingival overgrowth. J Clin Periodontol 23 : 165, 1996 https://doi.org/10.1111/j.1600-051X.1996.tb02072.x
  6. Seymour RA, Jacobs DJ : Cyclosporin and the gingival tissues. J Clin Periodontol 19 : 1, 1992 https://doi.org/10.1111/j.1600-051X.1992.tb01140.x
  7. David-Neto E, Lemos FB, Furusawa EA et al : Impact of cyclosporin A pharmacokinetics on the presence on side effects in pediatric renal transplantation. J Am Soc Nephrol 11 : 343, 2001
  8. Starzl TE, Weil R 3rd, Iwatsuki S et al : The use of cyclosporin A and prednisone in cadaver kidney transplantation. Surg Gynecol Obstet 151 : 17, 1980
  9. Ryffel B, Donatsch P, Madorin M et al : Toxicological evaluation of cyclosporin A. Arch Toxicol 53 : 107, 1983
  10. Rateitschak-pluss EM, Hefti A, Lortscher R et al : Intial observation that cylosprorin-A induces gingival enlargement in man. J Clin Periodontol 10 : 237, 1983 https://doi.org/10.1111/j.1600-051X.1983.tb01272.x
  11. Friskopp J, Klintmalm G : Gingival enlargement. A comparison between cyclosporine and azathioprine treated renal allograft recipients. Swed Dent J 10 : 85, 1986
  12. Tyldesley WR, Rotter E : Gingival hyperplasia induced by cyclosporin-A. Br Dent J 157 : 305, 1984 https://doi.org/10.1038/sj.bdj.4805474
  13. Emingil G, Coker I, Atilla G et al : Levels of leukotriene B4 and platelet activating factor in gingival crevicular fluid in renal transplant patients receiving cyclosporin-A. J Perodontol 71 : 50, 2000 https://doi.org/10.1902/jop.2000.71.1.50
  14. Yamada H, Nishimura F, Naruishi K et al : Phenytoin and cyclosporin A suppress the expression of MMP-1, TIMP-1, and cathepsin L, but not cathepsin B in cultured gingival fibroblasts. J Periodontol 71 : 955, 2000 https://doi.org/10.1902/jop.2000.71.6.955
  15. Bolzani G, Della Coletta R, Martelli Junior H et al : Cyclosporin A inhibits production and activity of matrix metalloproteinases by gingival fibroblasts. J Periodontal Res 35 : 51, 2000 https://doi.org/10.1034/j.1600-0765.2000.035001051.x
  16. Martelli-Junior H, Cotrim P, Graner E et al : Effect of transforming growth factor-beta1, interleukin-6, and interferon-gamma on the expression of type I collagen, heat shock protein 47, matrix metalloproteinase (MMP)-1 and MMP-2 by fibroblasts from normal gingiva and hereditary gingival fibromatosis. J Periodontol 74 : 296, 2003 https://doi.org/10.1902/jop.2003.74.3.296
  17. Cotrim P, de Andrade CR, Martelli-Junior H et al : Expression of matrix metalloproteinases in cyclosporintreated gingival fibroblasts is regulated by transforming growth factor (TGF)-beta1 autocrinestimulation. J Periodontol 73 : 1313, 2002 https://doi.org/10.1902/jop.2002.73.11.1313
  18. Hyland PL, Traynor PS, Myrillas TT et al : The effects of cyclosporin on the collagenolytic activity of gingival fibroblasts. J Periodontol 74 : 437, 2003 https://doi.org/10.1902/jop.2003.74.4.437
  19. Cotrim P, Martelli-Junior H, Graner E et al : Cyclosporin A induces proliferation in human gingival fibroblasts via induction of transforming growth factor-beta1. J Periodontol 74 : 1625, 2003 https://doi.org/10.1902/jop.2003.74.11.1625
  20. Schincaglia GP, Forniti F, Cavallini R et al : Cyclosporin- A increases type I procollagen production and mRNA level in human gingival fibroblasts in vitro. J Oral Pathol Med 21 : 181, 1992 https://doi.org/10.1111/j.1600-0714.1992.tb00098.x
  21. Das SJ, Newton HN, Olsen I : Keratinocyte growth factor receptor is up-regulated in cyclosporine A-induced gingival hyperplasia. J Dent Res 81 : 683, 2002 https://doi.org/10.1177/154405910208101006
  22. Maiola MP, McFadyen ML, Connolly C et al : Related Factors influencing phenytoin-induced gingival enlargement. J Clin Periodontol 27 : 506, 2000 https://doi.org/10.1034/j.1600-051x.2000.027007506.x
  23. Naidoo LC, Stephen LX : Nifedipine-induced gingival hyperplasia : non-surgical managment of a patients. Spec Care Dentist 19 : 29, 1999 https://doi.org/10.1111/j.1754-4505.1999.tb01365.x
  24. Tumini V, Di Placido G, D'Archivio D et al : Hyperplastic gingival lesions in pregnancy. I. Epidemiology pathology and clinical aspects. Minerva stomatol 47 : 159, 1998
  25. Weckx LL, Hidal LB, Marcucci G : Oral manifestations of leukemia. Far Nose Thoat J 69 : 341, 1990
  26. Stambaugh RV, Morgan AF, Enwonwu CO : Ascorbic acid deficiency associated with dilantin hyperplasia. J Periodontol 44 : 244, 1973 https://doi.org/10.1902/jop.1973.44.4.244
  27. Wirnsberger GH, Pfragner R, Mauric A et al : Effect of antibiotic treatment with azithromycin on cyclosporin Ainduced gingival hyperplasia among renal transplant recipient. Transplant Proc 30 : 2117, 1998
  28. Nash MM, Zaltzman JS : Efficacy of azithromycin in the treatment of cyclosproine-induced gingival hyperplasia in renal transplant recipients. Transplant Proc 65 : 1611, 1998
  29. Kohnle M, Lutkes P, Zimmermann U et al : Conversion from cyclosporinto tacrolimus in renal transplan recipients with gum hyperplasia. Tranplant Proc 31 : 44s, 1999
  30. Turkmen A, Ak G, Furuncuoglu Y et al : Relationship between gingival hyperplasia and class II histocompatibility antigens in renal transplant recipients. Nephron 84 : 29, 2000 https://doi.org/10.1159/000045535
  31. Atilla G, Sorsa T, Ronka H et al : Matrix Metalloproteinases (MMP-8 and -9) and neutrophil elastase in gingival crevicular fluid of cyclosporin-treated patients. J Periodontol 72 : 354, 2001 https://doi.org/10.1902/jop.2001.72.3.354
  32. Varga E, Mair LH : Medication influencing the development of gingival overgrowth renal transplant patients. Transplant Proc 30 : 2120, 1998
  33. Kohnle M, Lutkes P, Witzke O et al : Conversion to tacrolimus in cyclosporin A treated patients wit gum hyperplasia. Transplant Proc 30 : 2122, 1998
  34. Citterio F, Di Pinto A, Borzi MT et al : Azithromycin treatment of gingival hyperplasia in kidney transrecipients is effective and safe. Transplant Proc 33 : 2134, 2001