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.

Increased production of soluble TLR2 by lamina propria mononuclear cells from ulcerative colitis patients

“…TLR2 has been attributed with non-immune functions such as maintenance of intestinal homeostasis and protection from direct epithelial injury, likely by production of several factors (heatshock proteins, TNF, IL-6 and KC-1) (Rakoff-Nahoum et al 2004) involved in cytoprotection and tissue repair as KGF-1 , KGF-2 (Sanale et al 2002), TGF␤1 (van Tol et al 1999) and VEGF (Li et al 2001;Zheng et al 2002). Many of these factors are important in protection from gut injury (Podolsky 1999).…”

The Toll-Like Receptor Signaling Molecule Myd88 Contributes to Pancreatic Beta-Cell Homeostasis in Response to Injury

“…Components of microbial pathogens interact with TLRs to promote production of several protective factors relevant to cytoprotection, tissue repair and angiogenesis. These include TGF-β1 [8], VEGF [9], KGF-1 [10] KGF-2 [11], HGF [12] and prostaglandins [13].…”

Crucial Effects of Fibroblasts and Keratinocyte Growth Factor on Morphogenesis of Reconstituted Human Oral Epithelium

“…Although the connective tissue has been shown to have a general supportive e¡ect for the morpho-genesis of the overlying epithelial tissue (Mackenzie and Dabelsteen, 1987), the more speci¢c e¡ects of ¢broblasts on oral epithelial morphogenesis have not yet been fully addressed. It is known that oral ¢broblasts synthesize KGF (Dabelsteen et al, 1997;Sanale et al, 2002), and it has been proposed that oral ¢broblasts might be even more potent in producing KGF than their dermal counterparts (Okazaki et al, 2002;GrÖn et al, 2002). Exogenously added KGF stimulated cell proliferation in a study done on normal murine oral keratinocyte cell lines, but did not stimulate proliferation of neoplastic oral keratinocyte cell lines (Ning et al, 1998).…”