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

Proteases produced by Porphyromonas gingivalis, an oral pathogen, are considered important virulence factors and may affect the responses of cells equipped with proteinase-activated receptors. The aim of this study was to investigate the effect of the arginine-specific cysteine protease gingipain-R produced by P. gingivalis on chemokine production by human gingival fibroblasts (HGF) and the effect of gingipain-R treatment on the subsequent contact-dependent activation of HGF by T cells. HGF incubated in the presence of purified 47-kDa gingipain-R showed increased levels of interleukin-8 (IL-8) mRNA. Cyclooxygenase-2 (COX-2) mRNA was also induced. Further exposure of HGF to activated T cells resulted in the dose- and time-dependent enhancement of IL-8 transcription and release. T-cell membrane-bound tumor necrosis factor (TNF) was the ligand inducing IL-8 production by HGF, since TNF neutralization abrogated HGF responses to T-cell contact. The enhanced IL-8 release was due, at least in part, to prostaglandin-E(2) production, which was mostly blocked by indomethacin. Gingipain-R proteolytic activity was required since heat inactivation, specific synthetic protease inhibitors, and the natural substrate competitor histatin 5 abrogated its effects. The enhanced production of IL-8 in response to T-cell contact was specific since monocyte chemotactic protein-1 (MCP-1) production was unaffected while interferon-gamma-inducible protein-10 (IP-10) was inhibited. The sum of these activities may result in the recruitment of differential cell types to sites of inflammation since IL-8 preferentially recruits neutrophils and IP-10 attracts activated T cells and may be relevant to the pathogenesis of periodontitis.
 ...
PMID:Porphyromonas gingivalis gingipain-R enhances interleukin-8 but decreases gamma interferon-inducible protein 10 production by human gingival fibroblasts in response to T-cell contact. 1140 91

The interaction between epithelial cells and microorganisms is the most important step in bacterial infections. Actinobacillus actinomycetemcomitans was suggested to play a significant role in the initiation of periodontitis because of its bacteriological characteristics. Prostaglandins (PG) mediate the inflammatory response. Human beta-defensin-2 (hBD-2) is an antimicrobial peptide and contributes to innate immunity. E-cadherin is responsible for an epithelial intercellular junction. In this study, we investigated the syntheses of PGE2 and E-cadherin and the expression of hBD-2 in human gingival epithelial cells (HGEC) following exposure to A. actinomycetemcomitans. The levels of PGE2 and cyclooxygenase-2, which are responsible for an increase in PGE2, were increased depending on bacteria exposure time. hBD-2 mRNA was induced by A. actinomycetemcomitans, while HGEC exposed to A. actinomycetemcomitans showed a decrease in E-cadherin levels. Etodolac, a selective cyclooxygenase-2 inhibitor reinforced the increase in hBD-2 mRNA levels by A. actinomycetemcomitans. Furthermore, the etodolac suppressed the decrease in E-cadherin levels. Thus, endogenous PGE2 is involved in the hBD-2 and E-cadherin responses of HGEC to A. actinomycetemcomitans. These findings suggest that the inflammatory and antimicrobial response of gingival epithelial cells to A. actinomycetemcomitans is involved in the initiation of periodontal inflammation. A. actinomycetemcomitans may destroy the mechanical epithelial barrier by destroying E-cadherin.
 ...
PMID:Syntheses of prostaglandin E2 and E-cadherin and gene expression of beta-defensin-2 by human gingival epithelial cells in response to Actinobacillus actinomycetemcomitans. 1476 Sep 42

It is well established that prostaglandin E2 (PGE2) plays an important role in inflammatory diseases including periodontitis. Previously we have reported that the inflammatory mediators interleukin-1beta, (IL-1beta) and tumor necrosis factor alpha (TNFalpha) stimulate PGE2 synthesis by inducing mRNA expression of cyclooxygenase-2 (COX-2) in human gingival fibroblasts. In present study the involvement of microsomal prostaglandin E synthase-1 (mPGES-1) in relation to PGE2 production was investigated. The results showed that IL-1beta as well as TNFalpha induced mPGES-1 mRNA and protein expression accompanied by enhanced PGE2 production in gingival fibroblasts. The anti-inflammatory steroid dexamethasone (DEX) inhibited mPGES-1 mRNA and protein expression as well as PGE2 production induced by IL-1beta or TNFalpha. The COX-2 specific inhibitor, celecoxib, in contrast to the nonspecific COX inhibitor, indomethacin, markedly reduced mPGES-1 expression induced by IL-1beta. The results demonstrate that mPGES-1 regulates PGE2 production in gingival fibroblasts stimulated by inflammatory mediators IL-1beta and TNFa. This novel pathway may be a potential target for treatment strategies of periodontal disease.
 ...
PMID:Induction of microsomal prostaglandin E synthase-1 in human gingival fibroblasts. 1537 14

The objective was to review the literature on the effects of selective and non-selective non-steroidal anti-inflammatory drugs (NSAIDs) on the treatment of periodontal diseases. A search of MEDLINE was conducted and articles published in English until December 2003 were included. The results from in vitro and animal experiments as well as from human clinical trials are presented. Non-selective cyclooxygenase-1 (COX-1) inhibitors used in periodontal research include compounds such as aspirin, flurbiprofen, ibuprofen, naproxen and piroxicam. Selective cyclooxygenase-2 (COX-2) inhibitors represent a new group of pharmaceutical products termed "coxibs" that include meloxicam, nimesulide, etodolac and celecoxib. Evidence from animal experiments and clinical trials documents that selective and non-selective NSAIDs are mainly responsible for the stabilization of periodontal conditions by reducing the rate of alveolar bone resorption. This is achieved through local inhibition of both enzymes (e.g. COX-1 and COX-2) responsible for the synthesis of arachidonic acid metabolites. Evidence shows that the effects of NSAIDs drop off rapidly after drug withdrawal. One of the major advantages of selective COX-2 inhibition is the reduction of adverse systemic effects. Although some studies present promising results, no data from long-term, multicenter prospective clinical trials are yet available for determining whether these therapeutic effects can be retained on a long-term basis. Many of these compounds, such as flurbiprofen, are readily absorbed through the gingival tissues. Therefore, the development of topical NSAIDs formulations (e.g. gels, toothpastes, rinses) with a daily application seems to be of particular interest. This may help to further reduce adverse systemic effects of non-selective NSAIDs in the long-term host modulation of periodontitis-susceptible patients.
 ...
PMID:The effects of non-steroidal anti-inflammatory drugs (selective and non-selective) on the treatment of periodontal diseases. 1589 73

The aim of the present work was to evaluate the effect of a selective cyclooxygenase-2 (COX-2) inhibitor (meloxicam) on the alveolar bone loss progression in experimentally induced periodontitis. Forty (40) Wistar rats were separated into 8 experimental groups (n = 5). Cotton ligatures were placed at the gingival margin level of the lower right first molars of some rats. Four groups were treated for 5 or 15 days with an oral dose of 15 mg/kg of body weight/day of the selective COX-2 inhibitor. The other groups were used as positive control (sham) or negative control in each experimental period. Standardized digital radiographs were taken after sacrifice at 5 and 15 days to measure the amount of bone loss at the mesial root surface of the first molar tooth in each rat. The treatment with meloxicam did not induce weight alteration or other visible systemic manifestations. One way analysis of variance (ANOVA) indicated that groups treated with meloxicam, after 5 days, had significantly less alveolar bone loss (p < 0.05) when compared with control groups. On the other hand, no significant differences in bone loss were observed after 15 days of treatment with meloxicam. These data provide evidence that systemic therapy with meloxicam can modify the progression of experimentally induced periodontitis in rats during the initial experimental period.
 ...
PMID:Selective cyclooxygenase-2 inhibition prevents bone resorption. 1622 54

Butylated hydroxyanisole (BHA; a mixture of 2- and 3-BHA) is widely used as a potent antioxidant, but is reported to have adverse effects, such as carcinogenesis and pro-inflammatory activity, possibly due to the pro-oxidant property of this compound. 2-Methoxyphenol dimers derived from ferulic acid were recently demonstrated to inhibit the expression of lipopolysaccharide-stimulated cyclooxygenase-2 (COX-2) via redox-sensitive transcription factors such as nuclear factor kappa B or activator protein-1 (AP-1), due to a weakening of its pro-oxidant property by dimerization. To develop anti-inflammatory and/or anticancer drugs for the prevention of oral diseases, such as leukoplakia and destructive chronic periodontitis, whether 2-BHA (2-tert-butyl-4-methoxyphenol) and its synthetic ortho dimer, bis-BHA (3,3'-di-tert-butyl-5,5'-dimethoxy-1,1'-biphenyl-2,2'-diol) can inhibit AP-1 transcriptional activity stimulated by Porphyromonas gingivalis fimbriae was examined. The fimbria-stimulated AP-1 activation of RAW 264.7 murine macrophages was markedly inhibited by bis-BHA. However, BHA showed slight inhibition. Furthermore, bis-BHA significantly inhibited fimbria-induced COX-2 gene expression, which is closely involved with inflammation and carcinogenesis. These findings suggest that bis-BHA may possess a potent anti-inflammatory effect against oral diseases.
 ...
PMID:Preventive effect of ortho dimer of butylated hydroxyanisole on activator protein-1 activation and cyclooxygenase-2 expression in macrophages stimulated by fimbriae of Porphyromonas gingivalis, an oral anaerobe. 1688 13

We investigated the effect of etoricoxib, a selective cyclooxygenase-2 inhibitor, and indomethacin, a non-selective cyclooxygenase inhibitor, on experimental periodontitis, and compared their gastrointestinal side effects. A ligature was placed around the second upper left molars of female Wistar rats (160 to 200 g). Animals (6 per group) were treated daily with oral doses of 3 or 9 mg/kg etoricoxib, 5 mg/kg indomethacin, or 0.2 mL saline, starting 5 days after the induction of periodontitis, when bone resorption was detected, until the sacrifice on the 11th day. The weight and survival rate were monitored. Alveolar bone loss (ABL) was measured as the sum of distances between the cusp tips and the alveolar bone. The gastric mucosa was examined macroscopically and the periodontium and gastric and intestinal mucosa were examined by histopathology. The ongoing ABL was significantly inhibited (P < 0.05) by 3 and 9 mg/kg etoricoxib and by indomethacin: control = 4.08 +/- 0.47 mm; etoricoxib (3 mg/kg) = 1.89 +/- 0.26 mm; etoricoxib (9 mg/kg) = 1.02 +/- 0.14 mm; indomethacin = 0.64 +/- 0.15 mm. Histopathology of periodontium showed that etoricoxib and indomethacin reduced inflammatory cell infiltration, ABL, and cementum and collagen fiber destruction. Macroscopic and histopathological analysis of gastric and intestinal mucosa demonstrated that etoricoxib induces less damage than indomethacin. Animals that received indomethacin presented weight loss starting on the 7th day, and higher mortality rate (58.3%) compared to etoricoxib (0%). Treatment with etoricoxib, even starting when ABL is detected, reduces inflammation and cementum and bone resorption, with fewer gastrointestinal side effects.
 ...
PMID:Comparison of etoricoxib and indomethacin for the treatment of experimental periodontitis in rats. 1722 4

Eugenol is commonly used as an analgesic agent during acute pulpitis and is a major component of root canal sealers. Despite the frequent applications of eugenol in the practice of dentistry, little is known about the role of eugenol under the status of inflammation. This study was aimed to investigate the influence of eugenol on human macrophages (U937) under the stimulation of lipopolysaccharide (LPS). Eugenol was shown to block the release of the bone resorbing mediators, including interleukin-1beta (IL-1beta), tumor necrosis factor-alpha (TNF-alpha), and prostaglandin E2 from LPS-stimulated macrophages. In contrast, eugenol alone did not alter the expression levels of these proinflammatory mediators in macrophages. Consistent with downregulation of bone-resorbing mediators, eugenol suppressed the messenger RNA expression of LPS-induced IL-1beta, TNF-alpha, and cyclooxygenase-2 in macrophages. The results suggest a potential anti-inflammatory effect of eugenol in the acute inflamed pulps and apical periodontitis.
 ...
PMID:Eugenol suppressed the expression of lipopolysaccharide-induced proinflammatory mediators in human macrophages. 1750 9

Periodontal disease comprises a group of infections that lead to inflammation of the gingival and destruction of periodontal tissues and is accompanied by the loss of the alveolar bone with eventual exfoliation of the teeth. Porphyromonas gingivalis is a Gram-negative bacteria obtained from the periodontal pocket of patients with aggressive and chronic periodontitis. This bacteria presents in the external membrane lipopolysaccharide (LPS). Flavonoids are molecules obtained from plants and possess anti-inflammatory properties. Herein we characterize the effect of the flavonoids quercetin, genistein, luteolin, and quercetagetin on LPS-activated transduction mechanism regulation in human gingival fibroblasts (HGF). In this study, we investigated the role of the previously mentioned flavonoids on mitogen-activated protein kinase (MAPK) activation induced by LPS obtained from P. gingivalis. Our results showed that LPS treatment induces activation of extracellular signal related kinase 1/2 (ERK1/2), p38, and c-jun-NH(2)-terminal kinase (JNK). All flavonoids demonstrated an inhibitory effect on MAPK activation, interleukin, 1beta, and cyclooxygenase-2 (COX-2) expression, IL-1beta and prostaglandin E2 (PGE2) synthesis. The most active flavonoid was quercetagetin. Finally we found that the treatment with quercetagetin had no effect on cellular viability or in genetic material integrity.
 ...
PMID:The effect of flavonoids on transduction mechanisms in lipopolysaccharide-treated human gingival fibroblasts. 1763 Jan 99

Pro-inflammatory mediators formed by the kallikrein-kinin system can stimulate bone resorption and synergistically potentiate bone resorption induced by IL-1 and TNF-alpha. We have shown that the effect is associated with synergistically enhanced RANKL expression and enhanced prostaglandin biosynthesis, due to increased cyclooxygenase-2 expression. In the present study, the effects of osteotropic cytokines and different kinins on the expression of receptor subtypes for bradykinin (BK), des-Arg10-Lys-BK (DALBK), IL-1beta and TNF-alpha have been investigated. IL-1beta and TNF-alpha enhanced kinin B1 and B2 receptor binding in the human osteoblastic cell line MG-63 and the mRNA expression of B1 and B2 receptors in MG-63 cells, human gingival fibroblasts and intact mouse calvarial bones. Kinins did not affect mRNA expression of IL-1 or TNF receptors. EMSA showed that IL-1beta and TNF-alpha activated NF-kappaB and AP-1 in MG-63 cells. IL-1beta stimulated NF-kappaB via a non-canonical pathway (p52/p65) and TNF-alpha via the canonical pathway (p50/p65). Activation of AP-1 involved c-Jun in both IL-1beta and TNF-alpha stimulated cells, but c-Fos only in TNF-alpha stimulated cells. Phospho-ELISA and Western blots showed that IL-1beta activated JNK and p38, but not ERK 1/2 MAP kinase. Pharmacological inhibitors showed that NF-kappaB, p38 and JNK were important for IL-1beta induced stimulation of B1 receptors, and NF-kappaB and p38 for B2 receptors. p38 and JNK were important for TNF-alpha induced stimulation of B1 receptors, whereas NF-kappaB, p38 and JNK were involved in TNF-alpha induced expression of B2 receptors. These data show that IL-1beta and TNF-alpha upregulate B1 and B2 receptor expression by mechanisms involving activation of both NF-kappaB and MAP kinase pathways, but that signal transduction pathways are different for IL-1beta and TNF-alpha. The enhanced kinin receptor expression induced by the pro-inflammatory cytokines IL-1beta and TNF-alpha might be one important mechanism involved in the synergistic enhancement of prostaglandin formation caused by co-treatment with kinins and one of the two cytokines. These mechanisms might help to explain the enhanced bone resorption associated with inflammatory disorders, including periodontitis and rheumatoid arthritis.
 ...
PMID:Kinin B1 and B2 receptor expression in osteoblasts and fibroblasts is enhanced by interleukin-1 and tumour necrosis factor-alpha. Effects dependent on activation of NF-kappaB and MAP kinases. 1846 3


1 2 3 4 5 Next >>