Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P05231 (interleukin-6)
 23,907 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The oral commensal Gram-negative bacterium Actinobacillus actinomycetemcomitans is believed to be the causative organism of localized juvenile periodontitis, a disease in which there is rapid loss of alveolar bone supporting the teeth. Previously, we have reported that gentle saline extraction of this bacterium removed a loosely adherent proteinaceous fraction from the cell surface of the bacterium, which we have termed surface-associated material. This material contained potent bone-resorbing activity. We now report that surface-associated material is also a potent stimulator of cytokines, and in particular, interleukin-6 (IL-6) synthesis, while the lipopolysaccharide from this bacterium is only a weak stimulator of IL-6 synthesis by fibroblasts and monocytes. In contrast to enteric lipopolysaccharide (LPS), which induces fibroblast IL-1, IL-6 and tumour necrosis factor (TNF) alpha synthesis, surface-associated material stimulated gingival fibroblasts to synthesize only IL-6, with no induction of IL-1 or TNF (the normal inducers of IL-6 synthesis). Reverse transcriptase PCR also failed to detect mRNA for IL-1 or TNF in surface-associated-material-stimulated fibroblasts, although both mRNAs were present in Escherichia coli LPS-stimulated cells. Neutralizing antibodies to IL-1 and/or TNF or the natural IL-1 receptor antagonist (IL-1ra) inhibited enteric LPS-induced IL-6 synthesis, but did not inhibit surface-associated-material-induced synthesis. In addition, dexamethasone, which completely suppressed LPS-induced IL-6 synthesis, only inhibited surface-associated-material-induced IL-6 synthesis by 50%. This suggests that the active constituent in the surface-associated material stimulates IL-6 gene transcription by a transcriptional control mechanism distinct to that of E. coli LPS. The IL-6 stimulating activity of the surface-associated material is inhibited by both heat and trypsin, suggesting that it is proteinaceous. The activity has been isolated using anion-exchange, reverse-phase and size-exclusion HPLC. The active moiety is a peptide of molecular mass 2kDa which may be the product of a bacterial short open reading frame.
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PMID:Surface-associated material from the bacterium Actinobacillus actinomycetemcomitans contains a peptide which, in contrast to lipopolysaccharide, directly stimulates fibroblast interleukin-6 gene transcription. 866 8

Actinobacillus actinomycetemcomitans(Aa), elaborating a multiplicity of virulence factor and tissue-damaging products, is considered an etiological agent in periodontal disease. Serotype b is the most frequently isolated serotype in localized juvenile periodontitis patients, suggesting a particularly high periodontopathic potential for serotype b strains. Interleukin-6(IL-6) plays an important role in the mediation of inflammatory and immune responses as well as in the osteoclastic bone resorption. However, there is little information regarding the effect of the different serotypes of Aa on IL-6 production by human gingival fibroblasts (HGF). Therefore, the purpose of this study was to compare the ability of the three serotypes (a, b, and c) of Aa sonicates to induce the production of IL-6 by HGF. In fibroblast cultures, confluent monolayers of HGF were incubated with sonic extracts of Aa-511 (serotype a), Aa-Y4 (serotype b), and Aa-652 (serotype c) at various concentrations for 48 h at 37 degrees C in 5% CO2 and air. At the end of the culture period, supernatants were collected and analysed for IL-6 content by using EIA and bioassay. In order to compare the effects of non-lipopolysaccharide (LPS) activation of Aa sonicates on IL-6 production by HGF, we added polymyxin B in cultures with Aa sonicates to bind LPS. The results were summarized as follows. (1) All three serotypes of Aa sonicates had similar dose-dependent stimulant effects on IL-6 production by HGF, and the biological activities of IL-6 correlated with their immunoreactivities. (2) The maximum releases of IL-6 by HGF were achieved at concentrations of 10 to 100 micrograms protein/mL of Aa sonicates, and the ability of Aa-Y4 to induce the release of IL-6 was higher than that of Aa-511 and Aa-652 at these concentrations. (3) Polymyxin B (50 micrograms/mL) effectively decreased the amounts of IL-6 produced by stimulation of the HGF with 10 micrograms protein/mL of Aa sonicates. However, the polymyxin B-treated Aa-Y4 sonicate showed a higher ability to induce the release of IL-6 than the other two strains. These results indicate that Aa-Y4 (serotype b) has a higher potency to induce HGF secretion of IL-6; thus contributing to a comparatively stronger efficacy to the destruction of periodontal tissue in periodontitis.
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PMID:[Interleukin-6 production by human gingival fibroblasts following stimulation with Actinobacillus actinomycetemcomitans]. 971 39

Actinobacillus actinomycetemcomitans (A. actinomycetemcomitans) is supposed to be an important etiological agent in localized juvenile periodontitis (LJP). We have studied the effect of lipopolysaccharide (LPS) extracted from these periodontopathogenic bacteria on synthesis of the proinflammatory cytokines, interleukin-1beta(IL-1beta), tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6) and the anti-inflammatory cytokine IL-1 receptor antagonist (IL-1ra) in human whole blood. LPS from A. actinomycetemcomitans in concentrations > or =1 ng/ml induced a significant production of all these proinflammatory cytokines, whereas LPS from Escherichia coli (E. coli), strain 026:B6 had to be added in concentrations > or =1 microg/ml to obtain a similar effect. Similarly, LPS from A. actinomycetemcomitans > or =0.1 ng/ml resulted in production of IL-1ra, while LPS from E. coli 026:B6 had to be added at > or =10 ng/ml to obtain similar effects. It has been suggested that the ratio between production of proinflammatory and anti-inflammatory cytokines may influence the outcome of periodontal diseases. Other in vitro and in vivo studies have, however, indicated that very large excesses (100-1000 times) of IL-1ra compared to IL-1beta are required to shift the IL-1ra:IL-1beta ratio in favor of an inhibition of IL-1 bioactivity. In our ex vivo system, we found that stimulation with extremely low doses of A. actinomycetemcomitans LPS (0.1-1 ng/ml) resulted in IL-1ra production solely, without concomitant production of IL-1beta, the excess of IL-1ra over IL-1beta peaking at 1 ng/ml, which accordingly should suggest that LPS from A. actinomycetemcomitans primarily has proinflammatory effects.
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PMID:Lipopolysaccharide from Actinobacillus actinomycetemcomitans stimulates production of interleukin-1beta, tumor necrosis factor-alpha, interleukin-6 and interleukin-1 receptor antagonist in human whole blood. 1008 84