K. Watanabe et al., Association of mitogen-activated protein kinase pathways with gingival epithelial cell responses to Porphyromonas gingivalis infection, INFEC IMMUN, 69(11), 2001, pp. 6731-6737
Mitogen-activated protein (MAP) kinase pathways are key factors in host sig
naling events and can also play important roles in the internalization of p
athogenic bacteria by host cells. Porphyromonas gingivalis, a periodontal p
athogen, can efficiently invade human gingival epithelial cells (GECs). In
this study, we examined the activation of MAP kinase pathways in GECs infec
ted with P. gingivalis. c-Jun N-terminal kinase (JNK) was activated after 5
min of infection with P. gingivalis, whereas noninvasive Streptococcus gor
donii did not have a significant effect on JNK activation. In contrast, ext
racellular signal-regulated kinase (ERK) 1/2 was downregulated in a dose-de
pendent manner by P. gingivalis, but not by S. gordonii, after a 15-min exp
osure. Nonmetabolically active P. gingivalis cells were unable to modulate
MAP kinase activity. U0126, a specific inhibitor of MEK1/2 (ERK1/2 kinase),
and toxin B, a specific inhibitor of Rho family GTPases, had no effect on
P. gingivalis invasion. Genistein, a tyrosine protein kinase inhibitor, blo
cked uptake of P. gingivalis. The transcriptional regulator NF-kappaB was n
ot activated by P. gingivalis. These results suggest that P. gingivalis can
selectively target components of the MAP kinase pathways. ERK1/2, while no
t involved in P. gingivalis invasion of GECs, may be downregulated by inter
nalized P. gingivalis. Activation of JNK is associated with the invasive pr
ocess of P. gingivalis.