Porphyromonas gingivalis affects the collagen degrading ability of gingival fibroblast

Porphyromonas gingivalis (P. gingivalis) and matrix metalloproteinases (MMPs) are believed to play important roles in the tissue destruction associated with periodontal disease. In this dissertation, three studies aimed at understanding the effects that P. gingivalis has on human gingival fibroblasts (HGFs) mediated collagen degradation and the MMPs produced by these cells are discussed.;Culture supernatant from P. gingivalis ATCC 33277 increased the ability of HGFs to degrade Type I collagen. More active MMP-1, MMP-2, MMP-3, and MMP-14 were detected in the conditioned media from the HGFs treated with P. gingivalis culture supernatant than those from untreated HGFs. TIMP-1, but not TIMP-2, was decreased in the presence of P. gingivalis supernatant. MMP-1 mRNA expression increased more than two fold in the treated HGFs as compared to untreated HGFs.;The collagen degrading ability of multiple HGF cell lines treated with P. gingivalis supernatant was determined. In the presence of P. gingivalis supernatant, the collagen degrading ability of the HGFs was increased in 4 cell lines (aggressive) and was only slightly altered in the other 3 cell lines (non-aggressive). In the conditioned media from a P. gingivalis treated HGF aggressive cell line, MMP-1, MMP-2, and MMP-3 more readily underwent activation while the TIMP-1 protein level was decreased. None of these was altered in a non-aggressive cell line. It was concluded that heterogeneity exists in HGFs in regard to their collagen degrading ability in the presence of P. gingivalis .;Nicotine, a major pharmacologically active agent in tobacco, increased HGF mediated collagen cleavage. The membrane associated MMP-14 and MMP-2 produced by the nicotine treated HGFs more readily underwent zymogen activation. The TIMP-2 level was decreased in the culture media and increased in the cell membrane extracts. When the HGFs were treated with both nicotine and P. gingivalis supernatant, an additive effect on collagen cleavage was observed. These data suggest that nicotine promotes tissue destruction and adds to the detrimental effects of P. gingivalis on the extracellular matrix.;This project demonstrated some of the roles that P. gingivalis and the MMPs play in HGF mediated collagen degradation.