2009, Number 1
<< Back Next >>
Rev Odont Mex 2009; 13 (1)
Morphological and phenotypic differences in fibroblasts obtained from gingival overgrowth secondary to phenytoin: A pilot study
González OA, González JM
Language: English
References: 29
Page: 17-23
PDF size: 234.79 Kb.
ABSTRACT
Introduction: Gingival fibroblasts seem to be key cells in the pathogenesis of gingival overgrowth secondary to phenytoin intake. These cells not only participate in the extracellular matrix protein synthesis, but also regulate protein degradation through production of collagenolitic enzymes and phagocytosis. Some growth factors and cytokines such as IL-1a, TGF-b and TNF-a participate in the homeostasis of extracellular matrix.
Objective: The aim of this study was to evaluate the presence of IL-1a, TGF-b and TNF-a receptors on human gingival fibroblasts from a healthy donor, a patient with gingival overgrowth consuming phenytoin (responder) and a donor consuming phenytoin without gingival overgrowth (non- responder).
Methods and results: Primary cell cultures of gingival fibroblasts from each donor were characterized by flow cytometry demonstrating vimentin and CD14 positive cells. Using size detector, gingival fibroblasts from the responder donor were larger than fibroblasts from non-responder and healthy donor. A low but positive expression of IL-1R and TGF-bR was detected in cells from the responder donor. TNF-aR expression was detected in all three types of cultured cells but it was higher in the responder donor.
Conclusions: These results suggest differences in the morphologic and phenotypic characteristics between gingival fibroblasts from the donors studied.
REFERENCES
Modeer T, Dahllof G, Theorell K. Oral health in non-institutionalized epileptic children with special reference to phenytoin medication. Community Dent Oral Epidemiol 1986; 14(3): 165-168.
Pihlstrom BL, Carlson JF, Smith QT, Bastien SA, Keenan KM. Prevention of phenytoin associated gingival enlargement- a 15-month longitudinal study. J Periodontol 1980; 51(6): 311-317.
Aarli JA. Phenytoin-induced depression of salivary IgA and gingival hyperplasia. Epilepsia 1976; 17(3): 283-291.
Sooriyamoorthy M, Harvey W, Gower DB. The use of human gingival fibroblasts in culture for studying the effects of phenytoin on testosterone metabolism. Arch Oral Biol 1988; 33(5): 353-359.
Walsh LJ, Seymour GJ, Powell RN. The regulation of Langerhans cell T6, DR and DQ antigen expression: an hypotesis. J Oral Pathol 1988; 17(1): 43-46.
Hassell TM, Gilbert GH. Phenytoin sensitivity of fibroblasts as the basis for susceptibility to gingival enlargement. Am J of Pathol 1983; 112(2): 218-223.
Yamada H, Nishimura F, Naruishi K, Chou HH, Takashiba S, Albright GM, Nares S, Iacopino AM, Murayama Y. Phenytoin and Cyclosporin A supress the expression of MMP-1, TIMP-1 and cathepsin L, but not cathepsin B in cultured gingival fibroblasts. J Periodontol 2000; 71(6): 955-960.
Sasaki T, Maita E. Increased bFGF level in the serum of patients with phenytoin-induced gingival overgrowth. J Clin Periodontol 1988; 25(1): 42-47.
Modéer T, Mendez C, Dahllof G, Anduren I, Andersson G. Effect of phenytoin medication on the metabolism of epidermal growth factor receptor in cultured gingival fibroblasts. J Periodont Res 1990; 25(2): 120-127.
Brunius G, Yucel-Lindberg T, Shinoda K, Modeer T. Effect of phenytoin on interleukin-1 beta production in human gingival fibroblasts challenged to tumor necrosis factor alpha in vitro. Eur J Oral Sci 1996; 104(1): 27-33.
Tipton DA, Dabbous MK. Autocrine Transforming Growth Factor beta stimulation of extracellular matrix production by fibroblasts from fibrotic human gingiva. J Periodontol 1998; 69(6): 609-619.
Tomakidi P, Fusenig NE, Kohl A, Komposch G. Histomorphological and biochemical differentiation capacity in organotypic co-cultures of primary gingival cells. J Periodontal Res 1997; 32(4): 388-400.
González OA, Pereira R, Osorio G, González JM. Obtención y caracterización de un cultivo primario de fibroblastos gingivales humanos. Revista de la Facultad de Odontología, Universidad de Chile 2002; 20(2): 32-41.
Fries KM, Blieden T, Looney RJ, Sempowski GD, Silvera MR, Willis RA, Phipps RP. Evidence of fibroblast heterogeneity and the role of fibroblast subpopulations in fibrosis. Clin Immunol Immunopathol 1994; 72(3): 283-292.
Kuru L, Parkar MH, Griffiths GS, Newman HN, Olsen I. Flow cytometry analysis of gingival and periodontal ligament cells. J Dent Res 1998; 77(4): 555-564.
Shikata H, Utsumi N, Shimojima T, Oda Y, Okada Y. Increased expression of type VI collagen genes in drug-induced gingival enlargement. FEBS Lett 1993; 334(1): 65-68.
Tabeta K, Yamazaki K, Akashi S, Miyake K, Kumada H, Umemoto T, Yoshie H. Toll-like receptors confer responsiveness to lipopolysaccharide from Porphyromonas gingivalis in human gingival fibroblasts. Infect Immun 2000; 68(6): 3731-3735.
Watanabe A, Takeshita A, Kitano S, Hanazawa S. CD14-Mediated signal pathway of Porphyromonas gingivalis lipopolysaccharide in human gingival fibroblasts. Infect Immun 1996; 64(11): 4488-4494.
Hong HH, Uzel MI, Duan C, Sheff MC, Trackman PC. Regulation of lysyl oxidase, collagen, and connective tissue growth factor by TGF-beta1 and detection in human gingiva. Lab Invest 1999; 79(12): 1655-1667.
Mailhot JM, Schuster GS, Garnick JJ, Hanes PJ, Lapp CA, Lewis JB. Human periodontal ligament and gingival fibroblast response to TGF-beta 1 stimulation. J Clin Periodontol 1995; 22(9): 679-85.
Tewari DS, Qian Y, Tewari M, Pieringer J, Thornton RD, Taub R, Mochan EO. Mechanistic features associated with induction of metalloproteinases in human gingival fibroblasts by interleukin-1. Arch Oral Biol 1994; 39(8): 657-664.
Wright HJ, Chapple IL, Matthews JB. TGF-beta isoforms and TGF-beta receptors in drug-induced and hereditary gingival overgrowth. J Oral Pathol Med 2001; 30(5): 281-289.
Ito A, Mukaiyama A, Itoh Y, Nagase H, Thogersen IB, Enghild JJ, Sasaguri Y, Mori Y. Degradation of interleukin 1beta by matrix metalloproteinases. J Biol Chem 1996; 271(25): 14657-14660.
Cotrim P, de Andrade CR, Martelli-Junior H, Graner E, Sauk JJ, Coletta RD. Expression of matrix metalloproteinases in cyclosporin-treated gingival fibroblasts is regulated by transforming growth factor (TGF)-beta1 autocrine stimulation. J Periodontol 2002; 73(11): 1313-1322.
Domeij H, Yucel-Lindberg T, Modeer T. Signal pathways involved in the production of MMP-1 and MMP-3 in human gingival fibroblasts. Eur J Oral Sci 2002; 110(4): 302-306.
Johnson RB, Zebrowski EJ, Dai X. Synergistic enhancement of collagenous protein synthesis by human gingival fibroblasts exposed to nifedipine and interleukin-1-beta in vitro. J Oral Pathol Med 2000; 29(1): 8-12.
Noguchi K, Tominaga Y, Matsushita K, Izumi Y, Endo H, Kondo H, Ishikawa I. Upregulation of matrix metalloproteinase-1 production by prostaglandin F2alpha in human gingival fibroblasts. J Periodontal Res 2001; 36(5): 334-339.
Modeer T, Anduren I, Bengtsson A, Andersson G. Interleukin-1 beta and phenytoin reduce alpha 1 (I) procollagen mRNA expression in human gingival fibroblasts. J Periodontal Res 1996; 31(8): 563-569.
Johnson RB. Synergistic enhancement of collagenous protein synthesis by human gingival fibroblasts exposed to nifedipine and TNF-alpha in vitro. J Oral Pathol Med 2003; 32(7): 408-413.