Effect of lipopolysaccharide from periodontal pathogens on the production of tissue plasminogen activator and plasminogen activator inhibitor 2 by human gingival fibroblasts

Both tissue plasminogen activator (t-PA) and plasminogen activator inhibito r 2 (PAI-2) are important proteolysis factors present in inflamed human per iodontal tissues. The aim of the present study was to investigate the effec t of lipopolysaccharide (LPS) on the synthesis: of t-PA and PAI-2 by human gingival fibroblasts (HGF). LPS from different periodontal pathogens includ ing Actinobacillus actinomycetemcomitans, Porphyromonas gingivalis and Fuso bacterium nucleatum were extracted by the hot phenol water method. The leve ls of t-PA and PAI-2 secreted into the cell culture media were measured by enzyme-linked immunosorbent assays (ELISA). The mRNA for t-PA and PAI-2 wer e measured by RT-PCR. The results showed t-PA synthesis was increased in re sponse to all types of LPS studied and PAI-2 level was increased by LPS fro m A. actinomycetemcomitans and F. nucleatum, but not P. gingivalis. When co mparing the effects of LPS from non-periodontal bacteria (Escherichia coli and Salmonella enteritidis) with the LPS from periodontal pathogens, we fou nd that the ratio of t-PA to PAI-2 was greater following exposure of the ce lls to LPS from periodontal pathogens. The highest ratio of t-PA to PAI-2 w as found in those cells exposed to LPS from P. gingivalis. These results in dicate that LPS derived from periodontal pathogens may cause unbalanced reg ulation of plasminogen activator and plasminogen activator inhibitor by HGF and such an effect may, in part, contribute to the destruction of periodon tal connective tissue through dysregulated pericellular proteolysis.