This Article Abstract Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Saved Citations Download to citation manager Request Permissions Request Reprints Add to My Marked Citations Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Citing Articles via Scopus Google Scholar Articles by Nakao, K. Articles by Osaki, T. Search for Related Content PubMed PubMed Citation Articles by Nakao, K. Articles by Osaki, T. Social Bookmarking                         What's this?

Enhanced Cytokine Production and Collagen Synthesis of Gingival Fibroblasts from Patients with Denture Fibromatosis

Department of Oral Surgery, Kochi Medical School, Kohasu, Oko-cho, Nankoku-city, Kochi 783, Japan

K. Yoneda

Department of Oral Surgery, Kochi Medical School, Kohasu, Oko-cho, Nankoku-city, Kochi 783, Japan

T. Osaki

Department of Oral Surgery, Kochi Medical School, Kohasu, Oko-cho, Nankoku-city, Kochi 783, Japan

The mechanisms of denture-induced gingival hypertrophy remain to be explored. Since fibroblast proliferation and bone resorption characterize this disorder, the possible involvement of cytokines was investigated. Gingival fibroblasts were obtained from six patients with denture fibromatosis (Den-Fb) and six healthy persons (Nor-Fb). Cells were compared for proliferation, collagen synthesis, and cytokine production. Incorporation of [3H]thymidine (TdR) was increased in 3 Den-Fb and 3 Nor-Fb lines in the presence of interleukin-1-beta (IL-1β) (10 U/mL) and tumor necrosis factor-alpha (TNF-a) (from 10 to 100 U/mL). Proline incorporation in Den-Fb was higher than that in Nor-Fb, and the mean collagen synthesis level in Den-Fb was significantly higher than that in Nor-Fb. Although there was no difference between the up-regulation of protein synthesis in Den-Fb and Nor-Fb induced by IL-1β or TNF-a, the receptors for these cytokines were expressed at higher levels in cell lines which exhibited higher protein synthesis. Between Nor-Fb and Den-Fb, there was no difference in the generation of granulocyte-macrophage colony-stimulating factor (GM-CSF) or interleukin-6 (IL-6). However, most Den-Fb produced more GM-CSF and IL-6 in the presence of TNF-a. Enhancement of IL-6 generation by GM-CSF was also more prominent in Den-Fb. GM-CSF and IL-6 were synergistically generated after co-culture of the fibroblasts with gingival keratinocytes. GM-CSF and IL-6 generation of Den-Fb was markedly enhanced by co-culture of Den-Fb with peripheral blood mononuclear cells (PBMC), especially PBMC from patients. PBMC from patients generated more cytokines than did those from healthy subjects. These results indicate that cytokines generated in situ cooperatively by keratinocytes infiltrated mononuclear cells, and fibroblasts evoke up-regulation of collagen synthesis by fibroblasts expressing cytokine receptors.

Key Words: denture fibromatosis • fibroblasts • DNA synthesis • collagen synthesis • cytokines

REFERENCES

• Ala Y., Palluy O., Favero J., Bonne C., Modat G., Dornand J. (1992). Hypoxia/reoxygenation stimulates endothelial cells to promote interleukin-1 and interleukin-6 production. Effects of free radical scavengers. Agents Actions 37:134-139.[CrossRef][Medline] [Order article via Infotrieve]
• Bolton AE, Hunter WM (1973). The labelling of proteins to high specific radioactivities by conjugation to a 125I-containing acylating agent: Application to the radioimmunoassay. Biochem J 133:529-539.[Medline] [Order article via Infotrieve]
• Ellis JS, Seymour RA, Monkman S., Idle JR ( 1993). Disposition of nifedipine in plasma and gingival crevicular fluid in relation to drug-induced gingival overgrowth. J Periodont Res 28:373-378.[Medline] [Order article via Infotrieve]
• Gallo RL, Grabbe S., Choi SS, Bleicher P., Granstein RD (1992). Cyclosporin increases granulocyte/macrophage colony-stimulating factor (GM-CSF) activity and gene expression in murine keratinocytes. J Invest Dermatol 98:274-278.[CrossRef][Medline] [Order article via Infotrieve]
• Hajjar KA, Hajjar DP, Silverstein RL, Nachman RL (1987). Tumor
• necrosis factor-mediated release of platelet-derived growth factor from cultured endothelial cells. J Exp Med 166:235-245.
• Hori T., Kashiyama S., Hayakawa M., Shibamoto S., Tsujimoto M., Oku N., et al. (1989). Possible role of prostaglandins as negative regulators in growth stimulation by tumor necrosis factor and epidermal growth factor in human fibroblasts. J Cell Physiol 141:275-280.[CrossRef][Medline] [Order article via Infotrieve]
• Jilka RL, Hangoc G., Girasole G., Passeri G., Williams DC, Abrams JS, et al. (1992). Increased osteoclast development after estrogen loss: mediation by interleukin-6. Science 257:88-91.[Abstract/Free Full Text]
• Kawaguchi Y., Harigai M., Suzuki K., Hara M., Kobayashi K., Ishizuka T., et al. (1993). Interleukin 1 receptor on fibroblasts from systemic sclerosis patients induces excessive functional responses to interleukin lp. Biochem Biophys Res Commun 190:154-161.[CrossRef][Medline] [Order article via Infotrieve]
• Kimball ES, Fisher MC, Persico FJ (1988). Potentiation of Balb/3T3 fibroblast proliferative response by interleukin-1 and epidermal growth factor. Cell Immunol 113:341-349.[CrossRef][Medline] [Order article via Infotrieve]
• Kolde G., Schulze-Osthoff K., Meyer H., Knop J. ( 1992). Immunohistological and immunoelectron microscopic identification of TNF alpha in normal human and murine epidermis. Arch Dermatol Res 284:154-158.[CrossRef][Medline] [Order article via Infotrieve]
• Limat A., Hunziker T., Boillat C., Bayreuther K., Noser F. (1989). Post-mitotic human dermal fibroblasts efficiently support the growth of human follicular keratinocytes. J Invest Dermatol 92:758-762.[CrossRef][Medline] [Order article via Infotrieve]
• Lindemann RA, Economou JS, Rothermel H. (1988). Production of interleukin-1 and tumor necrosis factor by human peripheral monocytes activated by periodontal bacteria and extracted lipopolysaccharides. J Dent Res 67:1131-1135.
• Matsuki Y., Yamamoto T., Hara K. ( 1992). Detection of inflammatory cytokine messenger RNA (mRNA)-expressing cells in human inflamed gingiva by combined in situ hybridization and immunohistochemistry. Immunology 76:42-47.[Medline] [Order article via Infotrieve]
• Mizutani H., Black R., Kupper TS (1991). Human keratinocytes produce but do not process pro-interleukin-1 (IL-1) beta. Different strategies of IL-1 production and processing in monocytes and keratinocytes. J Clin Invest 87:1066-1071.[Medline] [Order article via Infotrieve]
• Pacifici R., Rifas L., Teitelbaum S., Slatopolsky E., McCracken R., Bergfeld M., et al. (1987). Spontaneous release of interleukin 1 from human blood monocytes reflects bone formation in idiopathic osteoporosis. Proc Natl Acad Sci USA 84:4616-4620.[Abstract/Free Full Text]
• Pfeilschifter J., Chenu C., Bird A., Mundy GR, Roodman GD (1989). Interleukin-1 and tumor necrosis factor stimulate the formation of human osteoclast-like cells in vitro. J Bone Miner Res 4:113-118.[Medline] [Order article via Infotrieve]
• Reinhardt RA, Masada MP, Kaldahl WB, DuBois LM, Kornman KS, Choi JI, et al. (1993). Gingival fluid IL-1 and IL-6 levels in refractory periodontitis. J Clin Periodontol 20:225-231.[CrossRef][Medline] [Order article via Infotrieve]
• Ross R., Raines EW, Bowen-Pope DF (1986). The biology of platelet-derived growth factor. Cell 46:155-169.[CrossRef][Medline] [Order article via Infotrieve]
• Shimizu N., Ogura N., Yamaguchi M., Goseki T., Shibata Y., Abiko Y., et al. (1992). Stimulation by interleukin-1 of interleukin-6 production by human periodontal ligament cells. Arch Oral Biol 37:743-748.[CrossRef][Medline] [Order article via Infotrieve]
• Sooriyamoorthy M., Gower DB, Eley BM ( 1990). Androgen metabolism in gingival hyperplasia induced by nifedipine and cyclosporin. J Periodont Res 25:25-30.[CrossRef][Medline] [Order article via Infotrieve]
• Sporn MB, Roberts AB (1988). Peptide growth factors are multifunctional. Nature 322:217-219.
• Stashenko P., Fujiyoshi P., Obernesser MS, Prostak L., Haffajee AD, Socransky SS (1991). Levels of interleukin 1 beta in tissue from sites of active periodontal disease. J Clin Periodontol 18:548-554.[CrossRef][Medline] [Order article via Infotrieve]
• Sugarman BJ, Agarwal BB, Hass PE, Figari IS, Pallandino MA Jr, Shepard HM (1985). Recombinant human tumor necrosis factor-p: effects on proliferation of normal and transformed cells in vitro. Science 230:943-945.[Abstract/Free Full Text]
• Thomson BM, Mundy GR, Chambers TJ (1987). Tumor necrosis factors β and a induce osteoblastic cells to stimulate osteoclastic bone resorption. J Immunol 138:775-779.[Abstract]
• Wahl SM, Costa GL, Mizel DE, Allen JB, Skaleric U., Mangan DF (1993). Role of transforming growth factor beta in the pathophysiology of chronic inflammation. J Periodontol 64:450-455.[Medline] [Order article via Infotrieve]
• Wang CY, Stashenko P. (1993). The role of interleukin-1 alpha in the pathogenesis of periapical bone destruction in a rat model system. Oral Microbiol Immunol 8:50-56.[Medline] [Order article via Infotrieve]
• Yamamoto T., Osaki T., Yoneda K., Ueta E. ( 1994). Cytokine-production by keratinocytes and mononuclear infiltrates in oral lichen planus. J Oral Pathol Med 23:309-315.[Medline] [Order article via Infotrieve]
• Yang Y., Tsai S., Wong GG, Clark SC (1988). Interleukin-1 regulation of hematopoietic growth factor production by human stromal fibroblasts. J Cell Physiol 134:292-296.[CrossRef][Medline] [Order article via Infotrieve]

Journal of Dental Research, Vol. 74, No. 4, 1072-1078 (1995)
DOI: 10.1177/00220345950740040701


CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    Twitter    What's this?

This article has been cited by other articles:

				G. PLENZ, H. ESCHERT, S. BEISSERT, V. ARPS, J. R. SINDERMANN, H. ROBENEK, and W. VOLKER Alterations in the vascular extracellular matrix of granulocyte macrophage colony-stimulating factor (GM-CSF) -deficient mice FASEB J, August 1, 2003; 17(11): 1451 - 1457. [Abstract] [Full Text] [PDF]

				L. W. Kent, F. Rahemtulla, R. D. Hockett Jr., R. C. Gilleland, and S. M. Michalek Effect of Lipopolysaccharide and Inflammatory Cytokines on Interleukin-6 Production by Healthy Human Gingival Fibroblasts Infect. Immun., February 1, 1998; 66(2): 608 - 614. [Abstract] [Full Text] [PDF]

This Article Abstract Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Saved Citations Download to citation manager Request Permissions Request Reprints Add to My Marked Citations Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Citing Articles via Scopus Google Scholar Articles by Nakao, K. Articles by Osaki, T. Search for Related Content PubMed PubMed Citation Articles by Nakao, K. Articles by Osaki, T. Social Bookmarking                         What's this?