Human beta defensin 3 alters matrix metalloproteinase production in human dendritic cells exposed to Porphyromonas gingivalis hemagglutinin B

Matrix metalloproteinases (MMPs) are zinc- or calcium-dependent proteinases involved in normal maintenance of extracellular matrix. When elevated, they contribute to the tissue destruction seen in periodontal disease. Recently, we found that human beta defensin 3 (HBD3), a cationic antimicrobial peptide, alters chemokine and proinflammatory cytokine responses in human myeloid dendritic cells exposed to Porphyromonas gingivalis hemagglutinin B (HagB). In this study, the hypotheses that HagB induces MMP production in dendritic cells and that HBD3 mixed with HagB prior to treatment alters HagB-induced MMP profiles were tested.

HagB was an MMP stimulus and HBD3 was found to decrease HagB-induced MMP1, -7, and -9 responses in dendritic cells at 16 hours, an observation that suggests HBD3 can alter microbial antigen-induced production of MMPs.

Dendritic cells were exposed to 0.2 μM HagB alone and HagB + HBD3 (0.2 or 2.0 μM) mixtures. After 16 hours, concentrations of MMPs in cell culture media were determined with commercial multiplex fluorescent bead-based immunoassays. An integrated cell network was used to identify potential HagB-induced signaling pathways in dendritic cells leading to the production of MMPs.

0.2 μM HagB induced MMP1, -2, -7, -9, and -12 responses in dendritic cells. 0.2 μM HBD3 enhanced the HagB-induced MMP7 response (P < 0.05) and 2.0 μM HBD3 attenuated HagB-induced MMP1, -7, and -9 responses (P < 0.05). The MMP12 response was not affected. In the predicted network, MMPs are produced via activation of multiple pathways. Signals converge to activate numerous transcription factors, which transcribe different MMPs.