PLC, p38/MAPK, and NF-κB-mediated induction of MIP-3α/CCL20 by Porphyromonas gingivalis

Macrophage inflammatory protein-3α/C-C chemokine ligand 20 (MIP-3α/CCL20) is an antimicrobial peptide that plays an important role in innate immunity. In addition to direct microbicidal effects, MIP-3α/CCL20 also exhibits cytokine-like functions that are critical during dendritic cell activation. The aim of the present study was to investigate further which signaling pathways are involved in the MIP-3α/CCL20 mRNA expression in response to whole-cell Porphyromonas gingivalis. Primary gingival epithelial cells (GECs) and the immortalized oral keratinocyte cell-line OKF6/TERT-2 were stimulated with whole-cell P. gingivalis. Prior to stimulation, GECs and OKF6/TERT-2 cells were pretreated with specific inhibitors for nuclear-factor-κB (NF-κB), mitogen-activated protein kinase (MAPK), phospholipase C (PLC), and phosphatidylinositol-3-kinase (PI3K). In GECs and OKF6/TERT-2 cells, activation of NF-κB was examined after exposure to P. gingivalis. The gene expression of MIP-3α/CCL20 was significantly induced in response to P. gingivalis (P ≤ 0.05) compared to unstimulated control cells. This induction was specifically blocked when cells were pre-incubated with inhibitors for NF-κB, MAPK, and PLC (P ≤ 0.05), but not for PI3K. These results demonstrate that P. gingivalis induces the MIP-3α/CCL20 mRNA in a NF-κB-, PLC-, and MAPK-dependent manner.