PKC, ERK/p38 MAP Kinases and NF-κB Targeted Signalling Play a Role in the Expression and Release of IL-1β and CXCL8 in Porphyromonas Gingivalis-infected THP1 Cells

Porphyromonas gingivalis is a keystone pathogen in periodontitis and is gaining importance in cardiovascular pathogenesis. Protease-activated receptors (PARs), toll-like receptors (TLRs) and nucleotide-binding oligomerization domain (NOD) on monocytes recognize the structural components on P. gingivalis, inducing inflammatory intermediates. Here, we elucidate the modulation of PARs, TLRs, NODs, and the role of MAPK and NF-κB in IL-1β and CXCL8 release. THP1 cells were stimulated with P. gingivalis wild-type W50 and its isogenic gingipain mutants: Rgp mutant E8 and Kgp mutant K1A. We observed modulation of PARs, TLRs, NOD, IL-1β and CXCL8 expression by P. gingivalis. Gingipains hydrolyse IL-1β and CXCL8, which is more evident for IL-1β accumulation at 24 h. Inhibition of PKC (protein kinase C), p38 and ERK (extracellular signal-regulated kinases) partially reduced P. gingivalis-induced IL-1β at 6 h, whereas PKC and ERK reduced CXCL8 at both 6 and 24 h. Following NF-κB inhibition, P. gingivalis-induced IL-1β and CXCL8 were completely suppressed to basal levels. Overall, TLRs, PARs and NOD possibly act in synergy with PKC, MAPK ERK/p38 and NF-κB in P. gingivalis-induced IL-1β and CXCL8 release from THP1 cells. These pro-inflammatory cytokines could affect leucocytes in circulation and exacerbate other vascular inflammatory conditions such as atherosclerosis.