Comparison of the pro-inflammatory cytokine-stimulating activity of the surface-associated proteins of periodontopathic bacteria.
Saline extraction of the periodontopathic bacterium, Actinobacillus actinomycetemcomitans, releases surface-associated material (SAM), a complex mixture of proteins and carbohydrates with potent biological actions on isolated bone and on various mammalian cell populations. In this study, the relative ability of the SAM from 5 organisms, implicated in the pathology of periodontal disease, to stimulate human mesenchymal and myelomonocytic cells to synthesize the proinflammatory cytokines - interleukin (IL)-1 beta, IL-6 and tumour necrosis factor (TNF)alpha has been investigated. The bacteria investigated were Actinobacillus actinomycetemcomitans, Eikenella corrodens, Porphyromonas gingivalis, Prevotella intermedia and Campylobacter rectus. Human cells were exposed to a four log order range of concentrations of the SAM, or of Escherichia coli lipopolysaccharide, to provide full agonist dose responses in order to allow comparison of the potency and efficacy of each SAM. All SAMs demonstrated the capacity to stimulate human gingival fibroblasts (HGFs), human peripheral blood mononuclear cells (PBMCs) or the myelomonocytic cell line - Mono-Mac-6 to release one or all of the cytokines assayed. Activity was heat- and trypsin-sensitive suggesting that the active components were proteinaceous. However, there were substantial differences in the potency and efficacy of each SAM when compared on a concentration basis (w/v). The most active SAM was from A. actinomycetemcomitans with those from E. corrodens and P. gingivalis being slightly less active. The least active cytokine-stimulating SAMs were from C. rectus and Pr. intermedia. One major difference between the SAMs and E. coli LPS was the inability of the former to stimulate HGFs to release IL-1 beta or TNF alpha although they could stimulate PBMCs to release these cytokines. This may have relevance to the pathology of the periodontal diseases.
Reddi
K
K
Maxillofacial Surgery Research Unit, Eastman Dental Institute, London, England.
Wilson
M
M
Nair
S
S
Poole
S
S
Henderson
B
B
D016976:Aggregatibacter actinomycetemcomitans / Q000502:physiology; D001426:Bacterial Proteins / Q000494:pharmacology* / Q000502:physiology; D002167:Campylobacter / Q000502:physiology; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis*; D016124:Eikenella corrodens / Q000502:physiology; D004926:Escherichia coli / Q000502:physiology; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D005881:Gingiva / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D006090:Gram-Negative Bacteria / Q000502:physiology*; D006801:Humans; D007375:Interleukin-1 / Q000096:biosynthesis; D015850:Interleukin-6 / Q000096:biosynthesis; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008648:Mesoderm / Q000187:drug effects / Q000378:metabolism; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism; D010510:Periodontal Diseases / Q000382:microbiology*; D016966:Porphyromonas gingivalis / Q000502:physiology; D018713:Prevotella intermedia / Q000502:physiology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D001426:Bacterial Proteins; D016207:Cytokines; D007375:Interleukin-1; D015850:Interleukin-6; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha