Inhibited proliferation of human periodontal ligament cells and gingival fibroblasts by Actinobacillus actinomycetemcomitans: involvement of the cytolethal distending toxin.
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.
Belibasakis
Georgios
G
Division of Oral Microbiology, Institute for Odontology, Umeå University, S-90187 Umeå, Sweden. george.belibasakis@odont.umu.se
Johansson
Anders
A
Wang
Ying
Y
Claesson
Rolf
R
Chen
Casey
C
Asikainen
Sirkka
S
Kalfas
Sotirios
S
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
D001427:Bacterial Toxins; D021122:Protein Subunits; C447141:cytolethal distending toxin, Actinobacillus actinomycetemcomitans; D004247:DNA