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

Abstract

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. Dendritic cells were exposed to 0.2 μM HagB alone and HagB + HBD3 (0.2 or 2.0 μM) mixtures. After 16hours, 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. HagB was an MMP stimulus and HBD3 was found to decrease HagB-induced MMP1, -7, and -9 responses in dendritic cells at 16hours, an observation that suggests HBD3 can alter microbial antigen-induced production of MMPs.