title: Keratinocyte growth factor (KGF)-1 and -2 protein and gene expression in human gingival fibroblasts.
abstract: The onset and progression of periodontal disease is associated with significant changes in the epithelial component of the attachment complex. From the early to the advanced stages of periodontal disease increased epithelial cell proliferation, migration and invasion into the surrounding connective tissue takes place. Concomitantly there is a significant increase in proinflammatory cytokine expression in periodontal tissue and quantitative and qualitative changes in the subgingival microflora, including an increase in gram-negative microorganisms. One of the most significant virulence factors of these bacteria is lipopolysaccharide (LPS) connected to the outer membrane. Two important growth factors controlling epithelial behavior are Keratinocyte Growth Factor-1 (KGF-1) and -2 (KGF-2). Connective tissue cells express these growth factors, but only epithelial cells respond to them. We studied the effect of proinflammatory cytokines and LPS on gingival fibroblast expression of KGF-1 and KGF-2 in vitro. Gingival fibroblasts were found to express KGF-1 and -2 in culture but only KGF-1 protein and gene expression was stimulated by serum, in a concentration-dependent manner by proinflammatory cytokines IL-1alpha, IL-1beta, TNF-alpha and IL-6 and LPS isolated from Porphyromonas gingivalis and Escherichia coli. The local increase in proinflammatory cytokine expression and the accumulation of LPS in disease sites may therefore stimulate gingival fibroblast expression of KGF-1. We hypothesize that this local increase in KGF-1 expression may, via a paracrine mechanism, stimulate local epithelial cell proliferation, migration and invasion during the onset and progression of periodontitis.
authors.affiliation: Department of Oral Biological and Medical Sciences, University of British Columbia, Vancouver, Canada.
authors.forename: Ali-Reza
authors.initials: AR
authors.lastname: Sanale
authors.forename: James D
authors.initials: JD
authors.lastname: Firth
authors.forename: Veli-Jukka
authors.initials: VJ
authors.lastname: Uitto
authors.forename: Edward E
authors.initials: EE
authors.lastname: Putnins
mesh_terms: D000911:Antibodies, Monoclonal; D015152:Blotting, Northern; D002455:Cell Division; D002460:Cell Line; D002465:Cell Movement; D004396:Coloring Agents; D018450:Disease Progression; D004797:Enzyme-Linked Immunosorbent Assay; D004847:Epithelial Cells / Q000378:metabolism; D004926:Escherichia coli; D051526:Fibroblast Growth Factor 10; D051523:Fibroblast Growth Factor 7; D005346:Fibroblast Growth Factors / Q000032:analysis* / Q000235:genetics; D005347:Fibroblasts / Q000378:metabolism*; D015870:Gene Expression; D005881:Gingiva / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology; D015850:Interleukin-6 / Q000494:pharmacology; D015603:Keratinocytes / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology; D018613:Microscopy, Confocal; D019899:Paracrine Communication; D010518:Periodontitis / Q000378:metabolism / Q000473:pathology; D016966:Porphyromonas gingivalis; D012333:RNA, Messenger / Q000032:analysis; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: D000911:Antibodies, Monoclonal; D004396:Coloring Agents; C496463:FGF10 protein, human; C496453:FGF7 protein, human; D051526:Fibroblast Growth Factor 10; D007375:Interleukin-1; D015850:Interleukin-6; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D051523:Fibroblast Growth Factor 7; D005346:Fibroblast Growth Factors