Enhancement of hepatocyte growth factor (scatter factor) production by human gingival fibroblasts in culture stimulated with Porphyromonas gingivalis fimbriae

Abstract

Hepatocyte growth factor (HGF), also known as scatter factor (SF), is a motogen, mitogen and morphogen produced by mesenchymal cells that mainly acts on epithelial cells and is involved in osteoclast stimulation. This study examined the possible enhanced production of HGF=SF by human gingival ®broblasts upon stimulation with killed cells of Porphyromonas gingivalis strain 381 and its representative bioactive cellular components, ®mbriae and lipopolysaccharide (LPS). P. gingivalis whole cells enhanced the production of HGF=SF detected by ELISA in culture supernates of the ®broblasts. Fimbriae prepared from P. gingivalis exhibited powerful HGF=SF-inducing activity in a concentration-dependent manner, with peak activity observed at 100±200 ìg=ml. The ®mbriae-induced HGF=SF mRNA expression by the cells was also detected by reverse transcription-PCR. P. gingivalis LPS exhibited weak HGF=SF-inducing activity. The study also examined the HGF=SF-inducing activity of seven synthetic peptides corresponding to the segments of P. gingivalis ®mbrial subunit protein. The peptides of residues 282±301 and 302±321, which exhibited antagonistic effects against P. gingivalis ®mbriae-binding to human gingival ®broblasts in a previous study, showed weak activity, whereas other non-antagonistic peptides showed no signi®cant activity. These ®ndings indicated that P. gingivalis ®mbriae enhanced production of HGF=SF by human gingival ®broblasts, whereas synthetic peptide segments of ®mbrial subunit protein were not suf®cient to exert the activity.

Hepatocyte Growth Factor Levels in Gingival Crevicular Fluid in Health, Disease, and After Treatment

“…Fibroblasts from human gingiva and normal dental pulp in culture are stimulated, in a dose‐dependent manner, to produce HGF by inflammatory cytokines, such as IL‐1α, IL‐1β, TNF‐α, 11 and PGE 2 12 . Furthermore, HGF is induced in gingival fibroblasts in culture by cell‐surface components of periodontitis‐associated bacteria, such as the fimbriae of P. gingivalis 14 . These observations suggest that the synthesis of HGF may increase in the gingiva with periodontitis as a mediator for regeneration; thus, HGF concentration might increase in GCF in periodontitis.…”

“…Furthermore, bacterial cell surface components, such as lipoteichoic acid, from various Gram‐positive bacteria and a glycoprotein portion from periodontopathogenic bacteria, Prevotella intermedia , 13 and fimbriae of Porphyromonas gingivalis , 14 induce HGF production in gingival fibroblasts in culture.…”

Improvement of Sepsis by Hepatocyte Growth Factor, an Anti-Inflammatory Regulator: Emerging Insights and Therapeutic Potential

“…Of interest, bacterial components, such as LPS from Gram-negative bacteria, protein A from Staphylococcus aureus , and fimbriae of Porphyromonas gingivalis stimulates HGF production in fibroblasts or macrophages through a transcriptional pathway [18, 49, 50]. Blood-born HGF can be stocked on surface of neutrophils, while LPS or TNF- α releases HGF from the cell surface (i.e., detachment mechanism) [51].…”

HGF Signaling Impacts Severity ofPseudomonas aeruginosaKeratitis

“…In periodontal disease, P. gingivalis LPS has been shown to enhance HGF production by human gingival fibroblasts. 47 This study implicated HGF and cmet in both the destructive and reparative phases of periodontal disease pathogenesis, as it is localized on both osteoclasts and osteoblasts. Escherichia coli LPS has been shown to stimulate the TLR4 pathway with concurrent HGF upregulation in septic patients with obstructive jaundice, 48 and in vitro kidney cell studies determined that HGF increased the invasiveness and cytotoxicity of P. aeruginosa.…”