title: Inhibited proliferation of human periodontal ligament cells and gingival fibroblasts by Actinobacillus actinomycetemcomitans: involvement of the cytolethal distending toxin.
abstract: Actinobacillus actinomycetemcomitans can inhibit fibroblast proliferation. The objective of this study was to characterize the early proliferative responses of human periodontal ligament cells (PDLC) and gingival fibroblasts (GF) to A. actinomycetemcomitans components and to investigate the possible involvement of the cytolethal distending toxin (cdt) produced by this bacterium. The PDLC and GF were challenged with surface components of A. actinomycetemcomitans. Both DNA and protein synthesis as well as cell lysis or apoptosis were assayed for a 6-h period after addition of the bacterial extract. Unlike the controls, inhibition of DNA synthesis had already occurred in the challenged cells at the end of the initial 3- to 6-h period. No lysis or apoptosis was detected, and the total protein synthesis remained unaffected. The persistence of the effect on cell growth was confirmed after a 72-h period of challenge, during which the cells remained viable but exhibited an elongated and distended cell body. No significant differences were observed between PDLC and GF. When a cdt-knockout strain of A. actinomycetemcomitans was used almost no inhibitory effect on cell proliferation was observed. It was concluded that A. actinomycetemcomitans causes a non-lethal inhibition of proliferation in PDLC and GF as a result of an early arrest of DNA synthesis. Cytolethal distending toxin is responsible for most of this effect. This bacterial property may compromise tissue homeostasis in the periodontium.
authors.affiliation: Division of Oral Microbiology, Institute for Odontology, Umeå University, S-90187 Umeå, Sweden. george.belibasakis@odont.umu.se
authors.forename: Georgios
authors.initials: G
authors.lastname: Belibasakis
authors.forename: Anders
authors.initials: A
authors.lastname: Johansson
authors.forename: Ying
authors.initials: Y
authors.lastname: Wang
authors.forename: Rolf
authors.initials: R
authors.lastname: Claesson
authors.forename: Casey
authors.initials: C
authors.lastname: Chen
authors.forename: Sirkka
authors.initials: S
authors.lastname: Asikainen
authors.forename: Sotirios
authors.initials: S
authors.lastname: Kalfas
mesh_terms: D016976:Aggregatibacter actinomycetemcomitans / Q000235:genetics / Q000502:physiology*; D017209:Apoptosis / Q000187:drug effects; D001427:Bacterial Toxins / Q000009:adverse effects* / Q000235:genetics; D018929:Cell Culture Techniques; D016923:Cell Death / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D048429:Cell Size / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004247:DNA / Q000096:biosynthesis / Q000187:drug effects; D005347:Fibroblasts / Q000187:drug effects* / Q000473:pathology; D005881:Gingiva / Q000187:drug effects* / Q000473:pathology; D006801:Humans; D016555:Matched-Pair Analysis; D009154:Mutation / Q000235:genetics; D010513:Periodontal Ligament / Q000187:drug effects* / Q000473:pathology; D021122:Protein Subunits / Q000009:adverse effects* / Q000235:genetics; D012044:Regression Analysis; D013223:Statistics as Topic; D013997:Time Factors
chemical_list: D001427:Bacterial Toxins; D021122:Protein Subunits; C447141:cytolethal distending toxin, Actinobacillus actinomycetemcomitans; D004247:DNA