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 aim of this study was to identify salivary immunoglobulin A (IgA) directed to oral microbial GroEL in patients with periodontitis and to demonstrate their potential protective role through a reduction of inflammatory cytokine production induced by microbial GroEL. Using five different proteins belonging to the heat-shock protein 60 family, Western immunoblot analysis of salivary IgA from 63 subjects revealed immunoreactivities with Campylobacter rectus GroEL and Porphyromonas gingivalis GroEL in subjects with periodontitis (P < 0.05) compared to control subjects. Using the BIACORE 1000 to measure the salivary IgA titers directed towards C. rectus GroEL, high resonance unit (RU) values were observed in the saliva samples from patients with periodontitis (P < 0.01). Furthermore, the number of teeth with deep pocket depth (>or=5 mm) showed a high correlation coefficient with the RU value (r = 0.50, P < 0.01). C. rectus GroEL possessed the ability to stimulate the production of interleukin-6 by gingival fibroblasts. Interestingly, salivary IgA antibody directed to C. rectus GroEL caused a partial inhibition of interleukin-6 production. This study showed a relationship between high levels of salivary IgA directed to GroEL and periodontal disease severity. Although additional investigations are required, salivary IgA to GroEL may have a protective role by reducing the inflammatory response induced by GroEL derived from periodontopathogenic bacteria.
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PMID:Salivary immunoglobulin A directed to oral microbial GroEL in patients with periodontitis and their potential protective role. 1692 27

Recent studies have suggested that the periodontal disease, chronic sub-clinical inflammation, is associated with atherosclerosis, although "cause or effect" relationship is still unclear. The aim of this study was to assess the association between the degree of periodontal infection and lipid profiles in diabetic subjects. Additionally, the association of such sub-clinical inflammation with HMG-CoA reductase gene expression was evaluated. One hundred and thirty-one non-obese relatively well-controlled Japanese type 2 diabetic patients were enrolled for the study. Although no significant association was observed between serum triglycerides, HLD-cholesterol and antibody titer to Porphyromonas gingivalis (Pg), the most predominant periodontal pathogen in adults, LDL-cholesterol was significantly associated with antibody titer to Pg. Concomitantly, the same works out to be true for total cholesterol. To understand the possible mechanisms underlying this association, we evaluated 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase gene expression in cultured HepG2 cells stimulated by either bacterial lipopolysaccharide (LPS) or inflammatory cytokines. Although Pg and E. coli LPS had no effect on HMG-CoA reductase gene expression, both tumor necrosis factor-alpha and interleukin-6 (IL-6), especially IL-6 at low concentration, markedly up-regulated HMG-CoA reductase gene expression. It can be concluded that Pg infection is associated with increased LDL-cholesterol in diabetic subjects, which may be accompanied by increased cholesterol synthesis by inflammatory cytokines.
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PMID:Periodontal infection and dyslipidemia in type 2 diabetics: association with increased HMG-CoA reductase expression. 1694 Dec 80

Metabolic syndrome and type 2 diabetes (T2DM) resulting from sustained hyperglycemia are considered as risk factors for cardiovascular disease (CVD) but the mechanism for their contribution to cardiopathogenesis is not well understood. Hyperglycemia induces nonenzymatic glycation of protein-yielding advanced glycation end products (AGE), which are postulated to stimulate interleukin-6 (IL-6) expression, triggering the liver to secrete tissue necrosis factor alpha (TNF-alpha) and C-reactive protein (CRP) that contribute to CVD pathogenesis. Although the high prevalence of periodontitis among individuals with diabetes is well known by dental researchers, it is relatively unrecognized in the medical community. The expression of the same proinflammatory mediators implicated in hyperglycemia (i.e., IL-6, TNF-alpha, and CRP) have been reported to be associated with periodontal disease and increased risk for CVD. We will review published evidence related to these 2 pathways and offer a consensus.
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PMID:Oral infection, hyperglycemia, and endothelial dysfunction. 1790 6

We recently reported an association between interleukin-6 (IL6) polymorphisms (SNPs) and haplotypes and aggressive periodontitis (AgP). The aim of this study was to investigate this association in a larger cohort of subjects, affected by either aggressive or chronic periodontitis. Five IL6 SNPs were analyzed in 765 subjects (167 generalized aggressive periodontitis, 57 localized aggressive, 310 chronic periodontitis and 231 periodontally healthy). Among Caucasians (n=454) there were moderate associations for -1363T allele (p=0.011) and for -174GG and -1363GG genotypes with diagnosis of periodontitis (respectively, p=0.044, OR=1.6, 95% CI=1.0-2.4, and p=0.017, OR=1.8, 95% CI=1.1-2.8, adjusted for age, gender and smoking). Haplotypes containing the -174G>C, -1363G>T and -1480C>G polymorphisms were associated with diagnosis of periodontitis (p=0.02). Subgroup analysis by disease phenotype showed associations for the localized AgP (LAgP) group and -1480C>G and -6106A>T SNPs (p=0.007 and 0.010, respectively). Among Caucasians the genotypes IL6 -1480 CC and -6106 TT increased the adjusted OR for LAgP (OR=3.09 and 2.27, respectively). This study supports the hypothesis that IL6 polymorphisms and haplotypes are moderately associated with periodontitis, possibly acting through influencing tissue levels of IL6. This association is stronger for LAgP than for other periodontal disease phenotypes.
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PMID:Association between periodontitis and common variants in the promoter of the interleukin-6 gene. 1908 30

Smokers are more susceptible than non-smokers to persistent infection by Porphyromonas gingivalis, a causative agent of periodontitis. Patients who smoke exhibit increased susceptibility to periodontitis and are more likely to display severe disease and be refractory to treatment. Paradoxically, smokers demonstrate reduced clinical inflammation. We show that P. gingivalis cells exposed to cigarette smoke extract (CSE) induce a lower proinflammatory response (tumour necrosis factor-alpha, interleukin-6, interleukin-12 p40) from monocytes and peripheral blood mononuclear cells than do unexposed bacteria. This effect is reversed when CSE-exposed bacteria are subcultured in fresh medium without CSE. Using microarrays representative of the P. gingivalis genome, CSE-exposure resulted in differential regulation of 6.8% of P. gingivalis genes, including detoxification and oxidative stress-related genes; DNA repair genes; and multiple genes related to P. gingivalis virulence, including genes in the major fimbrial and capsular operons. Exposure to CSE also altered the expression of outer membrane proteins, most notably by inducing the virulence factors RagA and RagB, and a putative lipoprotein cotranscribed with the minor fimbrial antigen. Therefore, CSE represents an environmental stress to which P. gingivalis adapts by altering gene expression and outer membrane proteins. These changes may explain, in part, the altered virulence and host-pathogen interactions that have been documented in vivo in smokers with periodontal disease.
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PMID:Tobacco-induced alterations to Porphyromonas gingivalis-host interactions. 1917 66

Recent research into periodontal disease pathology focuses on the role of receptor activator of nuclear factor-kappaB ligand (RANKL) and osteoprotegerin (OPG) in periodontal bone destruction processes. RANKL regulates the differentiation of osteoclast by binding to its specific receptor RANK, while OPG inhibits the differentiation of osteoclasts by binding RANKL and therefore preventing RANKL to bind RANK. The aim of the present study was to investigate the influence of Porphyromonas gingivalis lipopolysaccharide (LPS) and interleukin-6 (IL-6) on RANKL and OPG expression and release in periodontal ligament (PDL) cells. Human PDL cells were stimulated for 48 h with purified P. gingivalis LPS and IL-6. OPG and sRANKL release were assessed by using enzyme-linked immunosorbent assay technique. OPG and RANKL expression was quantitatively measured by using the real-time PCR technique. Whereas P. gingivalis LPS induced sRANKL release, expression was only slightly increased, IL-6 did not show an effect on RANKL expression or release. In conclusion the data demonstrate that stimulation of PDL cells with P. gingivalis LPS leads to an increased release of sRANKL, rather than increased RANKL expression. Through this action, P. gingivalis LPS may exert its biological effect on osteoclast formation and bone resorption.
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PMID:Influence of lipopolysaccharide and interleukin-6 on RANKL and OPG expression and release in human periodontal ligament cells. 1977 43

Veillonella parvula is an anaerobic gram-negative coccus that is part of the normal flora of the animal and human mouth and gastrointestinal and genitourinary tracts. Oral V. parvula is involved in the development of early periodontal disease as well as different types of serious infections. Present data on molecular mechanisms responsible for innate immune response against Veillonella are very scanty. The aim of this study was to investigate the Toll-like receptor (TLR) pathways responsible for V. parvula lipopolysaccharide (LPS) and to identify the intracellular pathways induced by this recognition. V. parvula LPS stimulated tumor necrosis factor alpha (TNF-alpha) and interleukin-6 (IL-6) release in human peripheral blood mononuclear cells (PBMC) in a dose-dependent manner. Pretreatment of cells with a TLR4 antagonist significantly reduced TNF-alpha and IL-6 production in PBMC stimulated with either Veillonella or Escherichia coli LPS. However, V. parvula LPS was 10- to 100-fold less active than E. coli LPS for cytokine induction. TNF-alpha, IL-1beta, IL-6, and IL-10 were released in wild-type and TLR2(-/-), but not TLR4(-/-), mouse macrophage cultures. V. parvula LPS was able to activate the human PBMC p38 mitogen-activated protein kinase (MAPK). A specific p38 MAPK inhibitor strongly inhibited V. parvula LPS-induced TNF-alpha, IL-1beta, IL-6, and IL-10. In conclusion, V. parvula LPS is able to induce cytokine production in both human and murine in vitro models, although it is less effective than Enterobacteriaceae LPS. V. parvula LPS-stimulated cytokine induction, as well as p38 MAPK activation, are TLR4-dependent features.
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PMID:Receptor recognition of and immune intracellular pathways for Veillonella parvula lipopolysaccharide. 1982 71

The most common oral diseases have a microbial aetiology. Pathogenic bacteria liberate a number of irritating agents including a lipopolysaccharide (LPS) that activates pro-inflammatory cytokines promoting increased activity of polymorphonucleocytes (PMN). Release of PMN-derived free radicals into an infected gingival area affects gums, periodontal ligaments and alveolar bone. Berries of Lonicera caerulea L. (blue honeysuckle) are rich in phenolics, particularly phenolic acids, flavonoids and anthocyanins that have multiple biological activities in vitro and in vivo such as antiadherence, antioxidant and anti-inflammatory. Studies have shown that polyphenols suppress a number of LPS-induced signals and thus could be effective against gingivitis. Here we assessed effects of the polyphenolic fraction of L. caerulea fruits (PFLC; containing 77% anthocyanins) on LPS-induced oxidative damage and inflammation in human gingival fibroblasts. Application of PFLC (10-50mug/ml) reduced reactive oxygen species (ROS) production, intracellular glutathione (GSH) depletion as well as lipid peroxidation in LPS-treated cells. PFLC treatment also inhibited LPS-induced up-regulation of interleukin-1beta (IL-1beta), interleukin-6 (IL-6) and tumour necrosis factor-alpha (TNF-alpha) and it suppressed expression of cyclooxygenase-2 (COX-2). The effects are presumably linked to its antioxidant and anti-inflammatory activities and suggest its use in attenuating the inflammatory process, including periodontal disease.
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PMID:Polyphenolic fraction of Lonicera caerulea L. fruits reduces oxidative stress and inflammatory markers induced by lipopolysaccharide in gingival fibroblasts. 2033 9

Bacterial lipopolysaccharide (LPS) release during periodontal infection is a significant component of periodontal disease. We hypothesized that some bacterial LPS release results from bacterial exposure to antibiotics. Therefore, we examined the ability of various classes of antibiotics to induce LPS release from Porphyromonas gingivalis as well as the ability of antimicrobial peptides (AMPs) to inhibit purified LPS. All antibiotics tested against P. gingivalis were able to liberate 1.9-12.9 times more LPS as compared to untreated bacteria. Among the three AMPs tested, LL-37 was found to be the most potent inhibitor of cytokine (tumor necrosis factor-alpha, interleukin-1beta, interleukin-6) production and completely neutralized purified P. ginigivalis LPS activity in the chromogenic limulus amebocyte lysate (LAL) and whole blood cytokine stimulation assays. These observations suggest that therapeutic approaches utilizing AMPs as adjuncts to neutralize released LPS should be considered.
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PMID:Antibiotic-induced Porphyromonas gingivalis LPS release and inhibition of LPS-stimulated cytokines by antimicrobial peptides. 2054 74

Porphyromonas gingivalis produces unusual sphingolipids that are known to promote inflammatory reactions in gingival fibroblasts and Toll-like receptor 2 (TLR2)-dependent secretion of interleukin-6 from dendritic cells. The aim of the present study was to examine whether P. gingivalis lipids inhibit osteoblastic function. Total lipids from P. gingivalis and two fractions, phosphoglycerol dihydroceramides and phosphoethanolamine dihydroceramides, were prepared free of lipid A. Primary calvarial osteoblast cultures derived from 5- to 7-day-old CD-1 mice were used to examine the effects of P. gingivalis lipids on mineralized nodule formation, cell viability, apoptosis, cell proliferation, and gene expression. P. gingivalis lipids inhibited osteoblast differentiation and fluorescence expression of pOBCol2.3GFP in a concentration-dependent manner. However, P. gingivalis lipids did not significantly alter osteoblast proliferation, viability, or apoptosis. When administered during specific intervals of osteoblast growth, P. gingivalis total lipids demonstrated inhibitory effects on osteoblast differentiation only after the proliferation stage of culture. Reverse transcription-PCR confirmed the downregulation of osteoblast marker genes, including Runx2, ALP, OC, BSP, OPG, and DMP-1, with concurrent upregulation of RANKL, tumor necrosis factor alpha, and MMP-3 genes. P. gingivalis total lipids and lipid fractions inhibited calvarial osteoblast gene expression and function in vivo, as determined by the loss of expression of another osteoblast differentiation reporter, pOBCol3.6GFPcyan, and reduced uptake of Alizarin complexone stain. Finally, lipid inhibition of mineral nodule formation in vitro was dependent on TLR2 expression. Our results indicate that inhibition of osteoblast function and gene expression by P. gingivalis lipids represents a novel mechanism for altering alveolar bone homeostasis at periodontal disease sites.
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PMID:Porphyromonas gingivalis lipids inhibit osteoblastic differentiation and function. 2058 77


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