Document Type

Thesis

Date of Degree

Spring 2014

Degree Name

MS (Master of Science)

Degree In

Oral Science

First Advisor

Dr. Kim A. Brogden

Abstract

Matrix metalloproteinases (MMP) are zinc- or calcium-dependent proteinases involved in the normal maintenance of the extracellular matrix. When elevated, MMPs degrade matrix components contributing to tissue destruction in infected periodontal sites.

The objectives of this study were two-fold: first to assess the ability of Porphyromonas gingivalis hemagglutinin B (HagB) to induce MMP responses in human myeloid dendritic cells and second, to assess the effect of host defense peptide human β defensin 3 (HBD3) to regulate and attenuate the MMP response of HagB treated dendritic cells. HBD3 (0.2, 2.0, or 20.0 µM) was given to primary dendritic cells pre-, co-, or post-treatment to HagB (0.02 or 0.2 µM). At 16 hours, MMP concentrations were determined. There were no significant differences in concentrations for all 3 replications for MMP-2 and -13. There were few significant differences in some of the replications for MMP-3, -7, and -9. There were more pronounced differences in MMP-1, -10, and -12 expression, which were significantly influenced by both the concentration of HBD3 and the timing of administration. Chemokine and cytokine responses were inversely related to MMP production. While MMP responses decreased in a dose related manner, chemokine responses were increased. Concentrations of MIP-1α were high and there were no differences in response to 0.02 and 0.2 M HagB with or without 20.0 M HBD3. However, the MIP-1β and TNFα response to 0.2 M HagB were only attenuated. HagB induces the production of MMPs in dendritic cells and treatment of dendritic cells with HBD3 can alter the profile of HagB-induced MMPs. Such a finding may have importance in the pathogenesis of periodontal disease.

Keywords

HagB, HDB3, MMP, Porphyromonas gingivalis

Pages

vii, 89 pages

Bibliography

Includes bibliographical references (pages 84-89).

Copyright

Copyright 2014 Monica Katherine Raina

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