Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0031099 (periodontitis)
 12,489 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Porphyromonas gingivalis (P. gingivalis) is implicated in the initiation and progression of periodontitis. Human gingival fibroblasts (HGFs) are the major constituent of gingival connective tissue. P. gingivalis or its components such as lipopolysaccharide (LPS) upregulate the production of various inflammatory cytokines including interleukin (IL)-1 and IL-6 in HGFs. Recently, we demonstrated that the binding of P. gingivalis LPS to Toll-like receptor 4 (TLR4) on HGFs activates various second messenger systems (Biochem. Biophys. Res. Commun. 273, 1161-1167, 2000). In the present study, we examined the level of TLR4 expression on HGFs by flow cytometric analysis (FACS), and studied the levels of IL-1 and IL-6 in the culture medium upon LPS stimulation of HGFs by enzyme-linked immunosorbent assay (ELISA). Upon stimulation by P. gingivalis LPS for 24 h, HGFs that expressed a high level of TLR4 secreted significantly higher levels of IL-1 and IL-6 than HGFs that expressed a low level of TLR4. On the other hand, after stimulation with P. gingivalis LPS for 24 h, the level of TLR4 on the surface of HGFs decreased. These results suggest that the level of TLR4 expression on HGFs reflects the extent of inflammation in the gingival tissue, and that P. gingivalis LPS downregulates TLR4 expression on HGFs. These findings may be used to control inflammatory and immune responses in periodontal disease.
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PMID:Heterogeneous expression of Toll-like receptor 4 and downregulation of Toll-like receptor 4 expression on human gingival fibroblasts by Porphyromonas gingivalis lipopolysaccharide. 1168 88

The aim of this study was to evaluate the local changes in the crevicular gingival fluid (CGF) determined by the inflammatory and immune response in periodontitis and gingivitis. The selected patients presented gingivitis (n = 9) and periodontitis: aggressive periodontitis (n = 21) and adult periodontitis (n = 8). The crevicular fluid was provided from the gingival and periodontal pocket. The measurement of PMN-elastase in the CGF, using the ELISA method, showed a significant (p < 0.01) increase of the enzyme concentration in the aggressive periodontitis group (62.1 +/- 3.91 ng/ml) comparing to the gingivitis group (33.04 +/- 4.14 ng/ml) but also the increase (p < 0.05) of this enzyme in the adult periodontitis (43.6 +/- 2.16 ng/ml) comparing to the gingivitis, which indicated the evolutive aspects of the inflammatory reaction in these diseases. The increased production of PMN-E is the result of the activation of polymorphonuclear cells (PMN) as a reaction of the microbial attack. Degranulation and release of proteolytic enzymes including elastase, which present cytotoxic capacities, follow the activation of neutrophil granulocytes (PMN). The activated granulocytes release proinflammatory cytokines IL-1, TNF-alpha which augment the inflammatory immune response. The aggressive periodontitis group showed an increased CGF level of IL-1 (780.4 +/- 104 pg/ml) comparing to the gingivitis group (275.5 +/- 78 pg/ml) (p < 0.01). TNF-alpha also presented an increased level (p < 0.01) in the aggressive periodontitis group (16.3 +/- 2.3 pg/ml) comparing to the gingivitis group (4.1 +/- 1.2 pg/ml) as a consequence of the periodontium destruction and of the tissular necrosis in the former group. In conclusion, our study shows a significant increase of the PMN-elastase and proinflammatory cytokines level in CGF of patients with gingivitis and periodontitis. The intensity of the inflammatory response in these diseases is strongly correlated to the activation of the neutrophil granulocytes which release these biological active molecules that could be used as evolution markers of the disease.
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PMID:Proinflammatory cytokines production and PMN-elastase release from activated PMN cells in the periodontal disease. 1184 41

Factors which increase the risk of severe adult periodontitis (AP) may also contribute to the success of dental implants. To determine which cytokines may be relevant, levels of interleukin-1alpha (IL-1alpha), interleukin-1beta (IL-1beta), interleukin-1 receptor antagonist (IL-1ra), interleukin-6 (IL-6) and interferon-gamma (IFN-gamma) mRNA were quantitated in gingival tissue from periodontitis patients and healthy controls. Periodontitis significantly increased levels of IL-1alpha, IL-1beta, IL-6 and IFN-gamma mRNA relative to healthy tissues. IL-1 was selected for further study, as it has inflammatory and bone resorbing properties. We examined IL-1A(-889) and IL-1B(+3953) alleles in Caucasian patients with AP and early-onset periodontitis (EOP), patients with dental implants and healthy individuals. The IL-1B(+3953) polymorphism was associated with AP. This was evident from an increased homozygosity for allele 2 in patients with AP and a decreased heterozygosity in advanced AP patients. IL-1A(-889) and a composite genotype [IL-1A(-889)2 plus IL-1B(+3953)2] showed no association with the incidence of periodontitis, disease onset or disease severity. IL-1A(-889), IL-1B(+3953) and the composite genotype also showed no association with failure of dental implants.
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PMID:Do interleukin-1 polymorphisms predict the development of periodontitis or the success of dental implants? 1185 58

Periodontal disease is the major cause of adult tooth loss and is commonly characterized by a chronic inflammation caused by infection of oral bacteria. Porphyromonas gingivalis (P. gingivalis) is one of the suspected periodontopathic bacteria and is frequently isolated from the periodontal pockets of patients with chronic periodontal disease. The lipopolysaccharide (LPS) of P. gingivalis is a key factor in the development of periodontitis. Gingival fibroblasts, which are the major constituents of gingival connective tissue, may directly interact with bacteria and bacterial products, including LPS, in periodontitis lesions. It is suggested that gingival fibroblasts play an important role in the host responses to LPS in periodontal disease. P. gingivalis LPS enhances the production of inflammatory cytokines such as interleukin (IL)-1, IL-6, IL-8, and tumor necrosis factor alpha (TNF-alpha) in gingival fibroblasts. However, the receptor that binds with P. gingivalis LPS on gingival fibroblasts remained unknown for many years. Recently, it was demonstrated that P. gingivalis LPS binds to gingival fibroblasts. It was also found that gingival fibroblasts express CD14, Toll-like receptor 4 (TLR4), and myeloid differentiation primary response gene 88 (MyD88). P. gingivalis LPS treatment of gingival fibroblasts activates several intracellular proteins, including protein tyrosine kinases, and up-regulates the expression of monocyte chemoattractant protein-1 (MCP-1), extracellular signal-regulated kinase 1 (ERK1), and signal-regulated kinase 2 (ERK2), IL-1 receptor-associated kinase (IRAK), nuclear factor-kappaB (NF-kappaB), and activating protein-1 (AP-1). These results suggest that the binding of P. gingivalis LPS to CD14 and TLR4 on gingival fibroblasts activates various second-messenger systems. In this article, we review recent findings on the signaling pathways induced by the binding of P. gingivalis LPS to CD14 and Toll-like receptors (TLRs) in gingival fibroblasts.
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PMID:Porphyromonas gingivalis lipopolysaccharide signaling in gingival fibroblasts-CD14 and Toll-like receptors. 1209 56

Periodontal disease is a significant cause of tooth loss among adults. It is initiated by pathogenic bacteria, which trigger an inflammatory response that is effective in preventing significant microbial colonization of the gingival tissues. In some individuals, the reaction to bacteria may lead to an excessive host response, resulting in periodontal tissue destruction. Recent developments suggest that interleukin (IL)-1 genetic polymorphisms may identify certain individuals who have a predisposed susceptibility to periodontal breakdown and that elevated levels of IL-1 are found in individuals with periodontal disease. However, there is no direct evidence that IL-1 per se is responsible for the critical events that occur in periodontitis. We investigated the role of IL-1 in periodontal disease in a Macaca fascicularis primate model, using human soluble IL-1 receptor type I as a specific inhibitor. The results indicate that inhibition of IL-1 alone significantly reduces inflammation, connective tissue attachment loss, and bone resorption that are induced by periodontal pathogens.
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PMID:Inflammation and tissue loss caused by periodontal pathogens is reduced by interleukin-1 antagonists. 1219 78

Interleukin (IL)-1 alpha, IL-1 beta and IL-1 receptor antagonist (ra) play a major role in regulation of the inflammatory response in periodontal tissues. The aim of this study was to investigate the distribution of genetic variation in the IL-1 gene family among periodontitis patients and controls, taking into account smoking and microbiology as additional variables. There were 53 non-smoking and 52 smoking patients with severe adult periodontitis and 53 periodontal healthy controls genotyped for genetic variation in the IL-1 gene family. The presence of Porphyromonas gingivalis and Actinobacillus actinomycetemcomitans was established by culture techniques. A higher frequency of genotype+ (IL-1A*2 + IL-1B*2 + IL-1RN*2) was found in non-smoking periodontitis patients in whom P. gingivalis and A. actinomycetemcomitans could not be detected (42.1% vs. 11.3% in controls; p = 0.0068; or 5.7, 95% ci: 1.6-19.8). This data provide evidence that polymorphisms in genes of the IL-1 family are associated with severe adult periodontitis and may be a risk factor for severe periodontitis.
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PMID:[Risk factors in adult periodontitis: polymorphism in the interleukin-1 gene family]. 1221 56

Hepatocyte growth factor (HGF), also known as scatter factor, is a broad-spectrum and multifunctional cytokine required for the development, growth and regeneration of various organs and tissues. The expression of HGF in human gingival fibroblasts is induced by inflammatory cytokines such as interleukin 1. Thus, although it is possible that content of HGF in gingival crevicular fluid (GCF) in periodontitis is increased, this has not so far been reported because the volume of GCF is too small to determine HGF by the available enzyme-linked immunosorbent assay (ELISA). A recently developed, highly sensitive ELISA for HGF, with a detection limit of 1 pg/ml sample, has now enabled HGF to be measured in GCF.The mean HGF content in GCF from sites with clinically healthy gingiva, defined by the absence of overt signs of gingival inflammation and a probing depth (PD) <3 mm, was 1.7 ng/ml, and that of periodontitis, defined by obvious alveolar bone loss detected by radiographic examination and a PD> or =3 mm, was 3.23 ng/ml. Although treating the periodontitis did not significantly decrease the HGF concentration despite significantly improved clinical scores such as PD and Gingival Index, the total amount of HGF in GCF did decrease significantly after treatment. HGF was expressed by gingival fibroblasts and inflammatory cells as determined by in situ hybridization. HGF-activator (HGFA), which converts inactive pro-HGF to active mature HGF, was detected in gingival epithelial cells by immunostaining. The expression of HGFA was also confirmed in gingival tissue by reverse transcription-polymerase chain reaction (RT-PCR). These findings indicate that HGF is synthesized and activated in gingiva that is clinically healthy or associated with periodontitis.
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PMID:Hepatocyte growth factor in gingival crevicular fluid and the distribution of hepatocyte growth factor-activator in gingival tissue from adult periodontitis. 1224 69

The aim of this controlled retrospective study was to evaluate the influence of an IL-1 gene polymorphism on the clinical and radiographic healing outcomes of GTR therapy. The study included 47 adult periodontitis patients with 94 deep intrabony defects treated by GTR using different membrane materials. The following clinical parameters were recorded at baseline and 12 months after surgery: papillary bleeding index (PBI), gingival recession (REC), probing pocket depth (PPD), clinical attachment level (CAL), and the vertical relative attachment gain (V-rAG). Bone changes in the defect regions due to GTR therapy were quantitatively evaluated using digital subtraction radiography (DSR). Polymorphisms of the IL-1A gene at position - 889 and of the IL-1B gene at position + 3953 were analyzed by PCR. Statistical analysis was performed using the Mann-Whitney-U and the Wilcoxon-Signed-Rank tests (alpha = 0.05). The study comprised 19 IL-1 genotype positive (IL-1 +) patients and 28 IL-1 genotype negative (IL-1 -) patients. Twelve months after GTR therapy, both patient groups revealed statistically significant PPD reductions and CAL gain [median (25/75% percentiles)]: Delta PPD [IL-1 + : 4.0 (2.5/5.0) mm; IL-1-: 3.8 (3.0/4.9) mm], Delta CAL [IL-1 + : 3.5 (3.0/4.8) mm; IL-1 -: 3.0 (1, 2/4, 5) mm]. V-rAG amounted to 60.0 (47.7/78.6)% in IL-1 + patients and 53.1 (43.4/81.9)% in IL-1 - patients. Both patient groups showed significant bone density gain in 40% (IL-1 +) and 43.6% (IL-1 -) of the initial defect area due to GTR. Neither the clinical nor the radiographic healing parameters revealed any statistically significant differences in the GTR healing outcome between IL-1 + and IL-1 - patients. In conclusion, these 12-month findings indicate that the IL-1 gene polymorphism has no influence on the clinical and radiographic regeneration results following GTR therapy.
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PMID:Influence of interleukin-1 gene polymorphism on periodontal regeneration in intrabony defects. 1255 33

Several studies have shown a role for interleukin-1 gene cluster polymorphisms in the risk assessment for periodontal diseases. In the Study of Health in Pomerania (SHIP), 3148 subjects were randomly selected from the population and assessed for a broad range of diseases and environmental/behavioral risk factors. From the complete study group in the age 40 to 60 years, N = 1085 subjects were genotyped for the interleukin-1 genotype composite polymorphism in relation to periodontal parameters. The study objective was to elucidate the gene-environment interaction between the risk factors smoking and IL-1 polymorphism. An increased risk of periodontal disease was found for IL-1 genotype-positive smokers: odds ratio adjusted for age, sex, education, and plaque OR = 2.50 (95% C.I. 1.21 to 5.13; p = 0.013). This was not the case with subjects who never smoked: OR = 1.09 (0.73-1.62; p = 0.676). These results support the hypothesis of gene-environmental interaction in periodontitis.
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PMID:The interleukin-1 polymorphism, smoking, and the risk of periodontal disease in the population-based SHIP study. 1259 47

Interleukin (IL)-1 and tumor necrosis factor (TNF) represent proinflammatory cytokines that stimulate a number of events which occur during periodontal disease. These include the induction of adhesion molecules and other mediators that facilitate and amplify the inflammatory response, the stimulation of matrix metalloproteinase, and bone resorption. The activity of these cytokines coincides with the critical events that occur during periodontal disease, namely, loss of attachment and bone resorption. The use of antagonists to IL-1 and TNF in experimental periodontitis have demonstrated a cause-and-effect relationship between the activity of these cytokines and the spread of an inflammatory front to deeper areas in the connective tissue, loss of connective tissue attachment, osteoclast formation, and loss of alveolar bone. In addition, the loss of fibroblasts that occurs during infection with periodontal pathogens is, in part, mediated by TNF. Thus, much of the damage that occurs during periodontal tissue destruction can be attributed to IL-1 and TNF activity. This destruction may very well represent an overreaction of the host response to periodontal pathogens caused by excessive production of IL-1 and TNF.
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PMID:The contribution of interleukin-1 and tumor necrosis factor to periodontal tissue destruction. 1271 Jul 61


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