title: Association of mitogen-activated protein kinase pathways with gingival epithelial cell responses to Porphyromonas gingivalis infection.
abstract: Mitogen-activated protein (MAP) kinase pathways are key factors in host signaling events and can also play important roles in the internalization of pathogenic bacteria by host cells. Porphyromonas gingivalis, a periodontal pathogen, can efficiently invade human gingival epithelial cells (GECs). In this study, we examined the activation of MAP kinase pathways in GECs infected with P. gingivalis. c-Jun N-terminal kinase (JNK) was activated after 5 min of infection with P. gingivalis, whereas noninvasive Streptococcus gordonii did not have a significant effect on JNK activation. In contrast, extracellular signal-regulated kinase (ERK) 1/2 was downregulated in a dose-dependent manner by P. gingivalis, but not by S. gordonii, after a 15-min exposure. 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, blocked uptake of P. gingivalis. The transcriptional regulator NF-kappaB was not activated by P. gingivalis. These results suggest that P. gingivalis can selectively target components of the MAP kinase pathways. ERK1/2, while not involved in P. gingivalis invasion of GECs, may be downregulated by internalized P. gingivalis. Activation of JNK is associated with the invasive process of P. gingivalis.
authors.affiliation: Department of Oral Biology, University of Washington, Seattle, Washington 98195, USA.
authors.forename: K
authors.initials: K
authors.lastname: Watanabe
authors.forename: O
authors.initials: O
authors.lastname: Yilmaz
authors.forename: S F
authors.initials: SF
authors.lastname: Nakhjiri
authors.forename: C M
authors.initials: CM
authors.lastname: Belton
authors.forename: R J
authors.initials: RJ
authors.lastname: Lamont
mesh_terms: D002070:Butadienes / Q000494:pharmacology; D002478:Cells, Cultured; D015536:Down-Regulation; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004847:Epithelial Cells / Q000166:cytology / Q000276:immunology / Q000382:microbiology; D005881:Gingiva / Q000166:cytology / Q000201:enzymology* / Q000276:immunology / Q000382:microbiology; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases; D020935:MAP Kinase Signaling System; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D009570:Nitriles / Q000494:pharmacology; D016966:Porphyromonas gingivalis / Q000276:immunology* / Q000472:pathogenicity; D048051:p38 Mitogen-Activated Protein Kinases
chemical_list: D002070:Butadienes; D004791:Enzyme Inhibitors; D016328:NF-kappa B; D009570:Nitriles; C113580:U 0126; D048031:JNK Mitogen-Activated Protein Kinases; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases