Mechanisms of <i>Actinobacillus Actinomycetemcomitans</i>‐Induced Expression of Interleukin‐8 in Gingival Epithelial Cells

Sfakianakis, Andreas; Barr, Charles; Kreutzer, D. L.

doi:10.1902/jop.2001.72.10.1413

Cited by 21 publications

(18 citation statements)

References 40 publications

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“…Numerous studies have analysed periodontal pathogens and their constituents to produce pro‐inflammatory cytokines. Extracts from A. actinomycetemcomitans have been able to induce IL‐8 in gingival epithelial cells independent of LPS (24). Comparison studies evaluating the ability of E. coli LPS and Porphyromonas gingivalis to induce IL‐6, IL‐8, IL‐10 and IL‐12 in dendritic cells found E. coli LPS to be the more potent agonist (12).…”

Section: Discussionmentioning

confidence: 99%

Actinobacillus actinomycetemcomitans lipopolysaccharide induces interleukin‐6 expression through multiple mitogen‐activated protein kinase pathways in periodontal ligament fibroblasts

Patil

Rossa

Kirkwood

2006

Oral Microbiology and Immunology

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Actinobacillus actinomycetemcomitans plays a major role in the pathogenesis of aggressive periodontitis. Lipopolysaccharide (LPS) derived from A. actinomycetemcomitans is a key factor in inflammatory cytokine generation within periodontal tissues. In this study, we identify major mitogen-activated protein kinase (MAPK) signaling pathways induced by A. actinomycetemcomitans LPS, Escherichia coli LPS and interleukin-1beta (IL-1beta) in a murine periodontal ligament (mPDL) fibroblast cell line. Immunoblot analysis was used to assess the phosphorylated forms of p38, extracellular-regulated kinase (ERK) and c-jun N-terminal kinase (JNK) MAPK following stimulation with A. actinomycetemcomitans LPS, E. coli LPS and IL-1beta. IL-6 mRNA induction was detected via reverse transcription-polymerase chain reaction, while protein levels were quantified via enzyme-linked immunosorbent assays (ELISA). We utilized biochemical inhibitors of p38, ERK and JNK MAPK to identify the MAPK signaling pathways needed for IL-6 expression. Additional use of stable mPDL cell lines containing dominant negative mutant constructs of MAPK kinase-3 and -6 (MKK-3/6) and p38 null mutant mouse embryonic fibroblast (MEF) cells were used to substantiate the biochemical inhibitor data. Blocking p38 MAPK with SB203580 reduced the induction of IL-6 mRNA by A. actinomycetemcomitans LPS, E. coli LPS and IL-1beta by >70%, >95% and approximately 60%, respectively. IL-6 ELISA indicated that blocking p38 MAPK reduced the IL-6 protein levels induced by A. actinomycetemcomitans LPS, E. coli LPS and IL-1beta by approximately 60%, approximately 50% and approximately 70%, respectively. All MAPK inhibitors significantly reduced the IL-6 protein levels induced by A. actinomycetemcomitans LPS, E. coli LPS and IL-1beta whereas only p38 inhibitors consistently reduced the A. actinomycetemcomitans LPS, E. coli LPS and IL-1beta induction of IL-6 mRNA steady-state levels. The contribution of p38 MAPK LPS-induced IL-6 expression was confirmed using MKK-3/6 dominant negative stable mPDL cell lines. Wild-type and p38alpha(-/-) MEF cells provided additional evidence to support the role of p38alpha MAPK in A. actinomycetemcomitans LPS-stimulated IL-6. Our results indicate that induction of IL-6 by E. coli LPS, IL-1beta and A. actinomycetemcomitans LPS requires signaling through MKK-3-p38alpha ERK, JNK and p38 MAPK in mPDL cells.

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Section: Discussionmentioning

confidence: 99%

Actinobacillus actinomycetemcomitans lipopolysaccharide induces interleukin‐6 expression through multiple mitogen‐activated protein kinase pathways in periodontal ligament fibroblasts

Patil

Rossa

Kirkwood

2006

Oral Microbiology and Immunology

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“…Functions of IL-8 are mediated through two receptors (CXCR1 and CXCR2); the expression was detected on numerous cell lineages, including neutrophils and epithelial cells [12]. Gingival epithelial cells (GEC) are capable of upregulating IL8 expression rapidly in response to A. actinomycetemcomitans challenge, facilitating thus the recruitment of neutrophils as a host defense mechanism [13, 14]. IL8 expression in GEC is induced by P. gingivalis [15] and T. forsythia [16]; IL-8 production by gingival fibroblast cultures is also affected by lipopolysaccharides of P. gingivalis and P. intermedia [17].…”

Section: Introductionmentioning

confidence: 99%

Haplotype Analysis of Interleukin-8 Gene Polymorphisms in Chronic and Aggressive Periodontitis

Linhartová

Vokurka

Poskerová

et al. 2013

Mediators of Inflammation

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Objectives. Periodontitis is an inflammatory disease characterized by connective tissue loss and alveolar bone destruction. Interleukin-8 (IL8) is important in the regulation of the immune response. The aim of this study was to analyze four polymorphisms in the IL8 gene in relation to chronic (CP) and aggressive (AgP) periodontitis. Methods. A total of 492 unrelated subjects were included in this case-control association study. Genomic DNA of 278 patients with CP, 58 patients with AgP, and 156 controls were genotyped, using the 5′ nuclease TaqMan assay, for IL8 (rs4073, rs2227307, rs2227306, and rs2227532) gene polymorphisms. Subgingival bacterial colonization was investigated by the DNA-microarray detection kit in a subgroup of subjects (N = 247). Results. Allele and genotype frequencies of all investigated IL8 polymorphisms were not significantly different between the subjects with CP and/or AgP and controls (P > 0.05). Nevertheless, the A(−251)/T(+396)/T(+781) and T(−251)/G(+396)/C(+781) haplotypes were significantly less frequent in patients with CP (2.0% versus 5.1%, P < 0.02, OR = 0.34, 95% CI: 0.15–0.78, resp., 2.0% versus 4.5%, P < 0.05, OR = 0.41, 95% CI: 0.18–0.97) than in controls. Conclusions. Although none of the investigated SNPs in the IL8 gene was individually associated with periodontitis, some haplotypes can be protective against CP in the Czech population.

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“…Proteases of P. gingivalis degrade expressed IL-8 (16). In addition, both A. actinomycetemcomitans and P. gingivalis are able to adhere to and invade primary and transformed epithelial cells (5,6,(17)(18)(19)(20).…”

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confidence: 99%

Influence of serum on interaction ofPorphyromonas gingivalisATCC 33277 andAggregatibacter actinomycetemcomitansY4 with an epithelial cell line

Guentsch¹,

Rönnebeck

Puklo

et al. 2010

Journal of Periodontal Research

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Mechanisms of Actinobacillus Actinomycetemcomitans‐Induced Expression of Interleukin‐8 in Gingival Epithelial Cells

Cited by 21 publications

References 40 publications

Actinobacillus actinomycetemcomitans lipopolysaccharide induces interleukin‐6 expression through multiple mitogen‐activated protein kinase pathways in periodontal ligament fibroblasts

Actinobacillus actinomycetemcomitans lipopolysaccharide induces interleukin‐6 expression through multiple mitogen‐activated protein kinase pathways in periodontal ligament fibroblasts

Haplotype Analysis of Interleukin-8 Gene Polymorphisms in Chronic and Aggressive Periodontitis

Influence of serum on interaction ofPorphyromonas gingivalisATCC 33277 andAggregatibacter actinomycetemcomitansY4 with an epithelial cell line

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