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Modulation of host matrix metalloproteinases by bacterial virulence factors relevant in human periodontal diseases
Objective:
Bacterial pathogens involved in periodontal diseases exert a part of their destructive effect by triggering and inducing host cells to elevate their secretion of matrix metalloproteinases (MMPs). Pathogen-secreted phospholipase (PLC) is one bacterial product that may trigger this host response. The roles of exogenous PLC leading to the release, secretion and expression of MMPs by peripheral blood neutrophils (PMNs), cultured epithelial cells of human gingiva and porcine periodontal ligament were investigated. Also the activities of PLC in the diseased and healthy gingival sulcular fluid (crevicular fluid, GCF) and molecular forms of gelatinases present in dental plaque were investigated.
Materials And Methods:
GCF, salivary and dental plaque samples were analyzed for PLC and proteinase activities. The abilities of PLC to induce PMNs and oral epithelial cells to release and express their MMPs were examined by specific functional, immunological and molecular biology means.
Results:
PMN-derived MMPs were found to predominate in periodontitis GCF and plaque, and PLC activities were higher in GCF of adult periodontitis patients than in healthy controls. Purified bacterial PLC (1 mU ml(-1)) efficiently induced PMN degranulation. PLC also induced MMP expression in the cultured epithelial cells. The strongest response was seen in MMP-9 and less in MMP-2. The induction was dose-dependent in the range of 0.0-1.0 U ml(-1) PI-PLC, and quiescent cultures were more responsive than proliferating ones. PLC induction of MMPs was polar, with increased levels of MMP-9 in the apical region and increased MMP-2 levels secreted in the basal direction. Northern analysis showed a strong increase in mRNA levels of MMP-9 and a smaller increase for MMP-2 and MMP-1. In the second part of the study we investigated the molecular forms of the released MMPs during periodontitis. In bacterial plaque of periodontitis patients the MMP-9 were found to be converted into lower molecular weight forms. Isolated proteinase from Porphyromonas gingivalis (ATCC 33277) was able to convert human proMMPs to their active forms.
Conclusion:
Bacterial PLC may induce degranulation of PMN MMPs and increase MMP expression in oral epithelial cells. The released proteases can be converted into active form by the proteases of plaque bacteria. Thereby, the pathogenic oral bacteria may indirectly participate in the destruction of periodontal tissues.
Insights
Bacterial phospholipase (PLC) from periodontal pathogens triggers host cells to release matrix metalloproteinases (MMPs), contributing to tissue destruction. These MMPs can be activated by plaque bacteria, exacerbating periodontal disease progression.
Area of Science:
- Periodontal medicine
- Microbiology
- Biochemistry
Background:
- Periodontal diseases involve bacterial pathogens that induce host cells to secrete matrix metalloproteinases (MMPs).
- Bacterial phospholipase (PLC) is a potential trigger for this host response, contributing to tissue damage.
Purpose of the Study:
- To investigate the role of exogenous bacterial PLC in inducing MMP release and expression by host cells.
- To analyze PLC activity in gingival crevicular fluid (GCF) and the molecular forms of gelatinases in dental plaque.
Main Methods:
- Analysis of GCF, saliva, and dental plaque for PLC and proteinase activities.
- Examination of PLC's ability to induce MMP release and expression in peripheral blood neutrophils (PMNs) and oral epithelial cells using functional, immunological, and molecular biology techniques.
Main Results:
- PLC activity was higher in GCF of periodontitis patients than in healthy controls.
- Bacterial PLC induced PMN degranulation and increased MMP expression (primarily MMP-9) in epithelial cells in a dose-dependent manner.
- Plaque bacteria, specifically Porphyromonas gingivalis, activated proMMPs, and MMP-9 was converted to lower molecular weight forms in periodontitis plaque.
Conclusions:
- Bacterial PLC contributes to periodontal tissue destruction by inducing PMN degranulation and increasing MMP expression in oral epithelial cells.
- Activated proteases from plaque bacteria can further degrade periodontal tissues, highlighting the indirect role of pathogenic bacteria in disease progression.