Periodontal ligament fibroblasts sustain destructive immune modulators of chronic periodontitis

Ahmed R. El-Awady, Regina L W Messer, Ahmed Y. Gamal, Mohamed M.H. Sharawy, Karl H. Wenger, Carol A. Lapp

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

Background: In healthy periodontal tissue, innate immune responses effectively confine and suppress a bacterial insult. However, a disruption of the host-bacterial equilibrium may produce an overexpression of cytokines and lead to permanent, host-mediated tissue damage. Although such periodontal destruction primarily results from activated immune mechanisms, the site-specific damage suggests that local tissues participate in these pathologic changes. Periodontal ligament fibroblasts (PDLFs) are prominent in the periodontium and are critical in homeostasis and regeneration because they have the ability to produce multiple cytokines in response to a bacterial insult. These cells could play a role in the local pathogenesis of periodontal disease. Methods: We studied alkaline phosphatase (ALP) activity, interleukin (IL)-6 production, and morphologic characteristics of cultured PDLFs that were isolated from periodontally healthy sites (H-PDLFs) and diseased sites (D-PDLFs) in humans. Quantitative analyses of 84 genes that are related to inflammation were performed using real-time polymerase chain reaction arrays. Results: A mineralizing medium induced a significant increase of ALP in H-PDLFs, but no significant enzymatic changes were detected in D-PDLFs after such treatment. The protein and gene expression of IL6 showed a significant upregulation in D-PDLFs, which also demonstrated a significant upregulation of 54% of genes in the inflammatory gene arrays. Conclusions: To our knowledge, these results represent the first biologic evidence that D-PDLFs retain uniquely inflammatory phenotypes that couldmaintain localized destructive signals in periodontitis. The overexpression of proinflammatory cytokines by PDLFs could amplify local inflammation by the continuous triggering of immune responses. In addition, the location of these cells could be critical in the progression of the inflammatory front into the deeper tissues. J Periodontol 2010; 81: 1324-1335.

Original languageEnglish (US)
Pages (from-to)1324-1335
Number of pages12
JournalJournal of Periodontology
Volume81
Issue number9
DOIs
StatePublished - Sep 1 2010

Fingerprint

Chronic Periodontitis
Periodontal Ligament
Fibroblasts
Periodontal Diseases
Cytokines
Alkaline Phosphatase
Interleukin-6
Up-Regulation
Genes
Inflammation
Periodontium
Periodontitis
Innate Immunity
Real-Time Polymerase Chain Reaction
Regeneration
Homeostasis
Phenotype
Gene Expression

Keywords

  • Cytokines
  • Fibroblasts
  • Gene expression
  • Innate immunity
  • Pathogenesis
  • Periodontal diseases

ASJC Scopus subject areas

  • Periodontics

Cite this

Periodontal ligament fibroblasts sustain destructive immune modulators of chronic periodontitis. / El-Awady, Ahmed R.; Messer, Regina L W; Gamal, Ahmed Y.; Sharawy, Mohamed M.H.; Wenger, Karl H.; Lapp, Carol A.

In: Journal of Periodontology, Vol. 81, No. 9, 01.09.2010, p. 1324-1335.

Research output: Contribution to journalArticle

El-Awady, Ahmed R. ; Messer, Regina L W ; Gamal, Ahmed Y. ; Sharawy, Mohamed M.H. ; Wenger, Karl H. ; Lapp, Carol A. / Periodontal ligament fibroblasts sustain destructive immune modulators of chronic periodontitis. In: Journal of Periodontology. 2010 ; Vol. 81, No. 9. pp. 1324-1335.
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abstract = "Background: In healthy periodontal tissue, innate immune responses effectively confine and suppress a bacterial insult. However, a disruption of the host-bacterial equilibrium may produce an overexpression of cytokines and lead to permanent, host-mediated tissue damage. Although such periodontal destruction primarily results from activated immune mechanisms, the site-specific damage suggests that local tissues participate in these pathologic changes. Periodontal ligament fibroblasts (PDLFs) are prominent in the periodontium and are critical in homeostasis and regeneration because they have the ability to produce multiple cytokines in response to a bacterial insult. These cells could play a role in the local pathogenesis of periodontal disease. Methods: We studied alkaline phosphatase (ALP) activity, interleukin (IL)-6 production, and morphologic characteristics of cultured PDLFs that were isolated from periodontally healthy sites (H-PDLFs) and diseased sites (D-PDLFs) in humans. Quantitative analyses of 84 genes that are related to inflammation were performed using real-time polymerase chain reaction arrays. Results: A mineralizing medium induced a significant increase of ALP in H-PDLFs, but no significant enzymatic changes were detected in D-PDLFs after such treatment. The protein and gene expression of IL6 showed a significant upregulation in D-PDLFs, which also demonstrated a significant upregulation of 54{\%} of genes in the inflammatory gene arrays. Conclusions: To our knowledge, these results represent the first biologic evidence that D-PDLFs retain uniquely inflammatory phenotypes that couldmaintain localized destructive signals in periodontitis. The overexpression of proinflammatory cytokines by PDLFs could amplify local inflammation by the continuous triggering of immune responses. In addition, the location of these cells could be critical in the progression of the inflammatory front into the deeper tissues. J Periodontol 2010; 81: 1324-1335.",
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AU - Lapp, Carol A.

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AB - Background: In healthy periodontal tissue, innate immune responses effectively confine and suppress a bacterial insult. However, a disruption of the host-bacterial equilibrium may produce an overexpression of cytokines and lead to permanent, host-mediated tissue damage. Although such periodontal destruction primarily results from activated immune mechanisms, the site-specific damage suggests that local tissues participate in these pathologic changes. Periodontal ligament fibroblasts (PDLFs) are prominent in the periodontium and are critical in homeostasis and regeneration because they have the ability to produce multiple cytokines in response to a bacterial insult. These cells could play a role in the local pathogenesis of periodontal disease. Methods: We studied alkaline phosphatase (ALP) activity, interleukin (IL)-6 production, and morphologic characteristics of cultured PDLFs that were isolated from periodontally healthy sites (H-PDLFs) and diseased sites (D-PDLFs) in humans. Quantitative analyses of 84 genes that are related to inflammation were performed using real-time polymerase chain reaction arrays. Results: A mineralizing medium induced a significant increase of ALP in H-PDLFs, but no significant enzymatic changes were detected in D-PDLFs after such treatment. The protein and gene expression of IL6 showed a significant upregulation in D-PDLFs, which also demonstrated a significant upregulation of 54% of genes in the inflammatory gene arrays. Conclusions: To our knowledge, these results represent the first biologic evidence that D-PDLFs retain uniquely inflammatory phenotypes that couldmaintain localized destructive signals in periodontitis. The overexpression of proinflammatory cytokines by PDLFs could amplify local inflammation by the continuous triggering of immune responses. In addition, the location of these cells could be critical in the progression of the inflammatory front into the deeper tissues. J Periodontol 2010; 81: 1324-1335.

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