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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
Author(s) -
Jayaprakash Kartheyaene,
Demirel Isak,
Gunaltay Sezin,
Khalaf Hazem,
Bengtsson Torbjörn
Publication year - 2017
Publication title -
apmis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.909
H-Index - 88
eISSN - 1600-0463
pISSN - 0903-4641
DOI - 10.1111/apm.12701
Subject(s) - porphyromonas gingivalis , mapk/erk pathway , chemokine , interleukin 8 , p38 mitogen activated protein kinases , microbiology and biotechnology , kinase , biology , protein kinase c , proinflammatory cytokine , receptor , signal transduction , chemistry , cytokine , inflammation , immunology , biochemistry , genetics , bacteria
Porphyromonas gingivalis is a keystone pathogen in periodontitis and is gaining importance in cardiovascular pathogenesis. Protease‐activated receptors ( PAR s), toll‐like receptors ( TLR s) and nucleotide‐binding oligomerization domain ( NOD ) on monocytes recognize the structural components on P. gingivalis , inducing inflammatory intermediates. Here, we elucidate the modulation of PAR s, TLR s, NOD s, and the role of MAPK and NF ‐κB in IL ‐1β and CXCL 8 release. THP 1 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 PAR s, TLR s, NOD , IL ‐1 β and CXCL 8 expression by P. gingivalis . Gingipains hydrolyse IL ‐1β and CXCL 8, 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 CXCL 8 at both 6 and 24 h. Following NF ‐κB inhibition, P. gingivalis ‐induced IL ‐1β and CXCL 8 were completely suppressed to basal levels. Overall, TLR s, PAR s and NOD possibly act in synergy with PKC , MAPK ERK /p38 and NF ‐κB in P. gingivalis ‐induced IL ‐1β and CXCL 8 release from THP 1 cells. These pro‐inflammatory cytokines could affect leucocytes in circulation and exacerbate other vascular inflammatory conditions such as atherosclerosis.