Cytokine Responses of Oral Epithelial Cells to Porphyromonas gingivalis Infection

Sandros, Jens; Karlsson, Christofer; Lappin, D.F.; Madianos, Phoebus N.; Kinane, Denis F.; Papapanou, Panos N.

doi:10.1177/00220345000790101301

Cited by 144 publications

(130 citation statements)

References 34 publications

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“…However, P. gingivalis has the ability to both adhere to and invade epithelial cells via a FimA-dependent process (17). Epithelial cells challenged with P. gingivalis secrete proinflammatory cytokines, including IL-6, IL-8, TNF-␣, IL-1␤, and GM-CSF (14,23). Our current findings suggest that FimA does not significantly contribute to the P. gingivalis-induced proinflammatory response in epithelial cells.…”

Section: Discussionmentioning

confidence: 70%

Differential Activation of Human Gingival Epithelial Cells and Monocytes by Porphyromonas gingivalis Fimbriae

2007

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Humans develop periodontitis in response to challenge by microbial dental plaque. Inflammation begins after perturbation of gingival epithelial cells by subgingival bacteria interacting through pattern-recognition receptors, including the Toll-like receptors (TLR). Porphyromonas gingivalis is a major periodontopathogen that interacts with epithelial cells through its cell surface fimbriae (FimA), leading to colonization and/or invasion. Previous work by our group has established membrane CD14 as an essential coreceptor for TLR2-mediated activation of transfected cell lines by P. gingivalis FimA. We have shown that gingival epithelial cells express TLR2 but not CD14 on their cell surfaces. We thus speculated that P. gingivalis FimA does not readily activate epithelial innate immune responses but rather functions to promote P. gingivalis colonization in the absence of a vigorous FimA-induced response. This hypothesis was verified by the findings that primary human gingival epithelial cells responded poorly to FimA in terms of interleukin (IL)-6, IL-8, granulocyte-macrophage colony-stimulating factor, and tumor necrosis factor alpha responses, in stark contrast to the marked response to other TLR2 agonists (Pam3Cys, FSL-1) that are not strictly dependent on CD14. On the other hand, CD14-expressing human primary monocytes responded with high levels of the same cytokines to both FimA and the control TLR2 agonists. The gingival epithelial cells failed to respond to FimA even in the presence of exogenously added soluble CD14. These data indicate that the gingival epithelial cell hyporesponsiveness to FimA is attributable to the lack of membrane-expressed but not soluble CD14. In conclusion, P. gingivalis FimA differentially activates human monocytes and epithelial cells, perhaps reflecting different tactics used by P. gingivalis when interacting with different host cell types or a host strategy to limit inflammation.Porphyromonas gingivalis is a gram-negative, black-pigmented bacterium associated with periodontal disease, a condition which results in destruction of the tooth-supporting tissues and loss of teeth (16). P. gingivalis expresses virulence factors involved in host tissue destruction and immune perturbation (10). Adhesion molecules of P. gingivalis include fimbriae (FimA) and hemagglutinins; however, P. gingivalis FimA is considered a critical determinant for the attachment of this microorganism in the oral cavity (16). In this regard, there is strong evidence supporting a crucial role for FimA in P. gingivalis adhesion to several mammalian cells types; indeed, nonfimbriated mutants of P. gingivalis, constructed by inactivation of the FimA gene, display reduced adhesion and invasion of epithelial cells compared to wild-type P. gingivalis (29). Moreover, nonfimbriated mutants display a reduced ability to induce periodontal disease in mice following oral inoculation (19). In this context, P. gingivalis FimA has been shown to induce proinflammatory cytokine release in macrophages (22) as well as inflammatory bon...

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Section: Discussionmentioning

confidence: 70%

Differential Activation of Human Gingival Epithelial Cells and Monocytes by Porphyromonas gingivalis Fimbriae

2007

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“…P. gingivalis, Treponema denticola, and Tannerella forsythia have been reported to suppress the production of this chemokine (7). Killing or protease treatments enhanced the capacity of P. gingivalis to elicit IL-8 (8, 9), although P. gingivalis did appear to induce a strong expression of IL-8 mRNA that was related to the capacity of the strain to adhere to and invade the epithelial cells (15). In this study, neither P. gingivalis biofilms nor planktonic challenge resulted in detectable IL-8 in the supernatants, as has been associated with gingipain degradation of the molecule (2).…”

mentioning

confidence: 99%

Epithelial Interleukin-8 Responses to Oral Bacterial Biofilms

Peyyala

Kirakodu

Novak

et al. 2011

Clin. Vaccine Immunol.

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“…Among the cytokines most consistently found to be associated with periodontitis are tumor necrosis factor alpha (TNF-␣), interleukin 1 (IL-1), IL-6, IL-8, and prostaglandin E2 (33). TNF-␣ is produced by various cell types, including fibroblasts, monocytes, lymphocytes, and epithelial cells (36). A range of bacterial components, such as lipopolysaccharide (LPS), are involved in the induction of TNF-␣ production (32,37).…”

mentioning

confidence: 99%

Long-Term Effect of Heat Shock Protein 60 from Actinobacillus actinomycetemcomitans on Epithelial Cell Viability and Mitogen-Activated Protein Kinases

Zhang¹,

Pelech

Uitto

2004

Infect Immun

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Our previous studies showed that bacterial heat shock protein 60 (hsp60) induces cultured epithelial cell proliferation within 24 h. Here we investigated the long-term effects of heat shock protein 60 isolated from Actinobacillus actinomycetemcomitans on skin keratinocyte (HaCaT cell line) viability and the cell signaling involved. Prolonged incubation in the presence of hsp60 increased the rate of epithelial cell death. The number of viable cells in hsp60-treated culture was 37% higher than the number in the control at 24 h but 27% lower at 144 h. A kinetics study of the effect of hsp60 on the phosphorylation of mitogen-activated protein kinases (MAPKs) involving Western blotting with phospho-specific antibodies showed that in addition to a transient early increase in p38 levels, a second peak appeared in keratinocytes 24 h after the addition of hsp60. In contrast, prolonged incubation with hsp60 caused a decrease in the level of phosphorylated extracellular signal-regulated kinase 1/2 (ERK1/2) compared with that in the controls, possibly as a result of protein phosphatase activity. We found that hsp60 increased the levels of several phosphatases, including MAP-2, which strongly dephosphorylates ERK1/2. Moreover, hsp60 increased the level of tumor necrosis factor alpha (TNF-␣) in culture medium in a dose-dependent manner. TNF-␣ added to culture showed a cytotoxic effect on epithelial cells, particularly with longer incubation periods. TNF-␣ also induced the phosphorylation of p38. Finally, our results show that bacterial hsp60 inhibited stress-induced synthesis of cellular hsp60. Therefore, several cell behavior changes caused by long-term exposure to bacterial hsp60 may lead to impaired epithelial cell viability.

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Cytokine Responses of Oral Epithelial Cells to Porphyromonas gingivalis Infection

Cited by 144 publications

References 34 publications

Differential Activation of Human Gingival Epithelial Cells and Monocytes by Porphyromonas gingivalis Fimbriae

Differential Activation of Human Gingival Epithelial Cells and Monocytes by Porphyromonas gingivalis Fimbriae

Epithelial Interleukin-8 Responses to Oral Bacterial Biofilms

Long-Term Effect of Heat Shock Protein 60 from Actinobacillus actinomycetemcomitans on Epithelial Cell Viability and Mitogen-Activated Protein Kinases

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