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)

During normal pregnancy, maternal hormones and locally acting cytokines play a key role in regulating the onset of labor, cervical ripening, uterine contraction, and delivery. Maternal infections during pregnancy have been demonstrated to perturb this normal cytokine and hormone-regulated gestation, sometimes resulting in preterm labor, preterm premature rupture of membranes, and preterm low birth weight (PLBW), i.e., < 2,500 g and < 37 weeks of gestation. Our research focus has been to determine whether periodontal infections can provide sufficient challenge to the mother to trigger PLBW. New experiments from 48 case-control subjects have measured gingival crevicular fluid (GCF) levels of PGE(2) and IL-1-beta to determine whether mediator levels were related to current pregnancy outcome. In addition, the levels of 4 periodontal pathogens were measured by using microbe-specific DNA probes. Results indicate that GCF-PGE(2) levels are significantly higher in PLBW mothers, as compared with normal birth weight (NBW) controls (131.4 +/- 21.8 vs. 62.6 +/- 10.3 [mean +/- SE ng/mL], respectively, at P = 0.02). Furthermore, within primiparous PLBW mothers, there was a significant inverse association between birth weight (as well as gestational age) and GCF-PGE(2) levels at P = 0.023. These data suggest a dose-response relationship for increasing GCF-PGE(2) as a marker of current periodontal disease activity and decreasing birth weight. Microbial data indicate that 4 organisms associated with mature plaque and progressing periodontitis--bacteroides forsythus, Porphyromonas gingivalis, Actinobacillus actinomycetemcomitans, and Treponema denticola--were detected at higher levels in PLBW mothers, as compared to NBW controls. These data suggest that biochemical measures of maternal periodontal status and oral microbial burden are associated with current PLBW.
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PMID:Potential pathogenic mechanisms of periodontitis associated pregnancy complications. 972 7

Patients with localized juvenile periodontitis (LJP) have elevated levels of immunoglobulin G2 (IgG2) in their sera. This is also observed in vitro when peripheral blood leukocytes from LJP patients are stimulated with pokeweed mitogen. In previous studies, we showed that lymphocytes from subjects with no periodontitis (NP subjects) produced substantial amounts of IgG2 when they were cultured with monocytes from LJP patients (LJP monocytes). These observations indicate that monocytes or monocyte-derived mediators are positive regulators of the production of IgG2. The present study was initiated to determine if secreted factors from LJP monocytes were capable of enhancing IgG2 production and to determine if prostaglandin E2 (PGE(2)), which LJP monocytes produce at elevated levels, enhances IgG2 production. Experiments in a transwell system and with monocyte-conditioned media indicated that cell-cell contact was not necessary for LJP monocytes to augment the production of IgG2 by T and B cells from NP subjects. Moreover, the production of IgG2 was selectively induced by the addition of PGE(2) or platelet-activating factor (PAF), another lipid cytokine, which can elevate PGE(2) synthesis. Furthermore, IgG2 production was abrogated when cells were treated with indomethacin, a cyclooxygenase inhibitor that blocks the synthesis of PGE(2), or the PAF antagonists CV3988 and TEPC-15. The effects of indomethacin were completely reversed by PGE(2), indicating that this is the only prostanoid that is essential for the production of IgG2. Similarly, PGE(2) reversed the effects of a PAF antagonist, suggesting that the effects of PAF are mediated through the induction of PGE(2) synthesis. Together, these data indicate that PGE(2) and PAF are essential for the production of IgG2.
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PMID:Regulation of immunoglobulin G2 production by prostaglandin E(2) and platelet-activating factor. 1067 75

The potential involvement of the inducible cyclooxygenase isoform (COX-2) and the role of novel lipid mediators were investigated in the pathogenesis of periodontal disease. Crevicular fluids from localized juvenile periodontitis (LJP) patients contained prostaglandin (PG)E(2) and 5-lipoxygenase-derived products, leukotriene B(4), and the biosynthesis interaction product, lipoxin (LX)A(4). Neutrophils from peripheral blood of LJP patients, but not from asymptomatic donors, also generated LXA(4), suggesting a role for this immunomodulatory molecule in periodontal disease. To characterize host responses of interest to periodontal pathogens, Porphyromonas gingivalis was introduced within murine dorsal air pouches. In the air pouch cavity, P. gingivalis elicited leukocyte infiltration, concomitant with elevated PGE(2) levels in the cellular exudates, and upregulated COX-2 expression in infiltrated leukocytes. In addition, human neutrophils exposed to P. gingivalis also upregulated COX-2 expression. Blood borne P. gingivalis gave significant increases in the murine tissue levels of COX-2 mRNA associated with both heart and lungs, supporting a potential role for this oral pathogen in the evolution of systemic events. The administration of metabolically stable analogues of LX and of aspirin-triggered LX potently blocked neutrophil traffic into the dorsal pouch cavity and lowered PGE(2) levels within exudates. Together, these results identify PMN as an additional and potentially important source of PGE(2) in periodontal tissues. Moreover, they provide evidence for a novel protective role for LX in periodontitis, limiting further PMN recruitment and PMN-mediated tissue injury that can lead to loss of inflammatory barriers that prevent systemic tissue invasion of oral microbial pathogens.
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PMID:Lipoxin A(4) analogues inhibit leukocyte recruitment to Porphyromonas gingivalis: a role for cyclooxygenase-2 and lipoxins in periodontal disease. 1076 33

Osteoclast differentiation factor (ODF), a recently identified cytokine of the TNF family, is expressed as a membrane-associated protein in osteoblasts and stromal cells. ODF stimulates the differentiation of osteoclast precursors into osteoclasts in the presence of M-CSF. Here we investigated the effects of LPS on the gene expression of ODF in mouse osteoblasts and an osteoblast cell line and found that LPS increased the ODF mRNA level. A specific inhibitor of extracellular signal-regulated kinase or protein kinase C inhibited this up-regulation, indicating that extracellular signal-regulated kinase and protein kinase C activation was involved. A protein synthesis inhibitor, cycloheximide, rather enhanced the LPS-mediated increase of ODF mRNA, and both a neutralizing Ab of TNF-alpha and a specific inhibitor of PGE synthesis failed to block the ODF mRNA increase by native LPS. Thus, LPS directly induced ODF mRNA. Mouse osteoblasts and an osteoblast cell line constitutively expressed Toll-like receptor (TLR) 2 and 4, which are known as putative LPS receptors. ODF mRNA increases in response to synthetic lipid A were defective in primary osteoblasts from C3H/HeJ mice that contain a nonfunctional mutation in the TLR4 gene, suggesting that TLR4 plays an essential role in the process. Altogether, our results indicate that ODF gene expression is directly increased in osteoblasts by LPS treatment via TLR, and this pathway may play an important role in the pathogenesis of LPS-mediated bone disorders, such as periodontitis.
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PMID:Gene expression of osteoclast differentiation factor is induced by lipopolysaccharide in mouse osteoblasts via Toll-like receptors. 1120 18

Previous studies have analyzed the lymphoid and myeloid foci within the gingival mucosa in health and chronic periodontitis (CP); however, the principal APCs responsible for the formation and organizational structure of these foci in CP have not been defined. We show that in human CP tissues, CD1a(+) immature Langerhans cells predominantly infiltrate the gingival epithelium, whereas CD83(+) mature dendritic cells (DCs) specifically infiltrate the CD4(+) lymphoid-rich lamina propria. In vivo evidence shows that exacerbation of CP results in increased levels of proinflammatory cytokines that mediate DC activation/maturation, but also of counterregulatory cytokines that may prevent a Th-polarized response. Consistently, in vitro-generated monocyte-derived DCs pulsed with Porphyromonas gingivalis strain 381 or its LPS undergo maturation, up-regulate accessory molecules, and release proinflammatory (IL-1beta, PGE(2)) and Th (IL-10, IL-12) cytokines. Interestingly, the IL-10:IL-12 ratio elicited from P. gingivalis-pulsed DCs was 3-fold higher than that from Escherichia coli-pulsed DCs. This may account for the significantly (p < 0.05) lower proliferation of autologous CD4(+) T cells and reduced release of IFN-gamma elicited by P. gingivalis-pulsed DCs. Taken together, these findings suggest a previously unreported mechanism for the pathophysiology of CP, involving the activation and in situ maturation of DCs by the oral pathogen P. gingivalis, leading to release of counterregulatory cytokines and the formation of T cell-DC foci.
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PMID:Mature dendritic cells infiltrate the T cell-rich region of oral mucosa in chronic periodontitis: in situ, in vivo, and in vitro studies. 1159

Alveolar bone destruction is a characteristic feature of periodontitis. Treponema denticola is known to be involved in periodontitis. To elucidate the role of T. denticola in alveolar bone destruction in periodontitis, the effects of lipooligosaccharide (LOS) from T. denticola on osteoclast formation and on expression of osteoclast differentiation factor (ODF) and osteoprotegerin (OPG) mRNAs were examined in a coculture system by using mouse calvaria and bone marrow cells. In addition, the effect of T. denticola LOS on expression of matrix metalloproteinases (MMPs), which are involved in bone resorption, was estimated in mouse calvaria-derived osteoblastic cells. When the mouse calvaria and bone marrow cells were challenged with LOS (0.1 to 10 micro g/ml) for 4 days, the number of tartrate-resistant acid phosphatase-positive multinucleated cells increased in a dose-dependent manner. The expression of ODF mRNA increased, while OPG mRNA expression decreased. Polymyxin B changed the effect of LOS (10 micro g/ml) on ODF and OPG mRNA expression to the control level. LOS (10 micro g/ml) stimulated prostaglandin E(2) (PGE(2)) production in the cocultures. Adding indomethacin, an inhibitor of prostaglandin synthesis, resulted in a reduction in the number of osteoclasts induced by LOS and eliminated the effect of T. denticola LOS on ODF and OPG mRNA expression. T. denticola LOS increased the levels of mRNAs encoding MMP-3, -8, -9, -10, -13, and -14. Expression of one of these mRNAs, MMP-9 mRNA, was significantly induced by T. denticola LOS. These findings suggest that LOS from T. denticola stimulates osteoclastogenesis and MMP expression. Up-regulation of ODF and down-regulation of OPG by a PGE(2)-dependent mechanism were involved in the osteoclastogenesis induced by T. denticola LOS.
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PMID:Induction of osteoclastogenesis and matrix metalloproteinase expression by the lipooligosaccharide of Treponema denticola. 1249 70

Prostaglandin E2 (PGE2) exerts its biological actions via EP receptors (EP1, EP2, EP3, and EP4). In the present study, we investigated whether PGE2 regulated interleukin (IL)-1beta-induced matrix metalloproteinase (MMP)-3 production in human gingival fibroblasts (HGF) derived from periodontally healthy subjects and diseased patients. In HGF from healthy gingiva, PGE2 down-regulated IL-1beta-induced MMP-3 production, whereas in HGF from periodontitis patients, PGE2 enhanced it. Butaprost (an EP2 agonist) and ONO-AE1-329 (an EP4 agonist) suppressed IL-1beta-induced MMP-3 production, and 17-phenyl-omega-trinor PGE2 (an EP1 agonist) mimicked the PGE(2) effect in HGF from healthy and periodontally diseased tissues, respectively. Analysis of these data suggests that, in HGF from healthy tissue, IL-1beta-induced MMP-3 production is down-regulated by PGE2 via EP2 and EP4 receptors, whereas in cells from periodontally diseased tissue, IL-1beta-induced MMP-3 production is up-regulated via EP1 receptors. Different regulation of IL-1beta-induced MMP-3 production by PGE2 between healthy and periodontally diseased tissues may be involved in the pathogenesis of periodontal disease.
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PMID:Prostaglandin E2 regulates interleukin-1beta-induced matrix metalloproteinase-3 production in human gingival fibroblasts. 1498 Nov 31

OBJECTIVE: Study the effects of Gu Chi paste on PGE(2) in gingiva and alveolar bone and its mechanism to treating periodontitis. METHODS: Periodontitis were formed with silk thread suture and high sugar diet,fed guinea pigs on Gu Chi paste and indomethacin.The prostaglandin E(2)(PGE(2)) in gingiva and alveolar bone were measured with radioimmunoassay (RIA). RESULTS: The Gingival Index(GI) and Pocket Deep(PD) of group Periodontitis (PE) were bigger than group Normal(N),the alveolar bone absorbed more severe,the PGE(2) level in gingiva and alveolar bone in PE was higherthan that in N.The GI and PD of group Gu Chi paste(Gu) were lower than that of PE,its alveolar bone absorbed more slight.There were more significant difference of PGE(2) in alveolar bone between Gu and group indomethacin(IND).The PGE(2) level of Gu in gingiva were similar as that of IND. CONCUSION: Gu Chi paste can inhibite the formation of experimental periodontitis and the contents of PGE(2) in gingiva and alveolar bone,and the effect on PGE(2) in alveolar was more severe. The mechanism of Gu Chi paste to periodontitis has inhibitory effects on PGE(2) in gingiva and alveolar bone.
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PMID:[Effects of Gu Chi paste on PGE(2) in periodontitis tissues of guinea pigs] 1507 24

This investigation analyses the contents of prostaglandin E(2)(PGE(2)),6-keto-prostaglandin F(1a)(6-k-PGF(1a)) and thromboxane B(2)(TXB(2)) in gingival fibroblast (GF) and periodontal ligament cell(PDLC) by microspectrophotometer.The results showed that the absorbance of PGE(2) in GF was 0.25+/-0.03,the absorbance of 6-k-PGF(1a) was 0.20+/-0.03,there were significant difference between PGE(2),6-k-PGF(1a) and control group.The absorbance of PGE(2),TXB(2) and 6-k-PGF(1a) and control group.The absorbance of PGE(2),TXB(2) and 6-k-PGF(1a) in PDLC each were 0.20+/-0.20,0.16+/-0.03 and 0.13+/-0.02.They were much bigger than control group(0.07+/-0.01),which indicated prostaglandins in GF and PDLC can affect guided tissue regeneration and gingivitis degree,and there were important relationship between PG(s) in GF,PDLC and periodontitis.
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PMID:[Analysing the contents of prostaglandins in gingival fibroblast and periodontal ligament cell by microspectrophotometer] 1516 79

Periodontitis, an inflammatory disorder of the supporting tissue of teeth, is one of the most common infectious diseases in humans. Periodontal pathogens promote inflammatory cytokines such as interleukin-1 (IL-1) and prostaglandin E2 (PGE2), resulting in alveolar bone destruction. In the present study, we examined the cellular and molecular mechanisms of IL-1-induced osteoclastogenesis using a coculture system of human periodontal ligament (PDL) cells and mouse spleen cells. IL-1alpha induced tartrate-resistant acid phosphatase positive (TRAP+) cell formation in a dose-dependent manner. IL-1alpha up-regulated receptor activator of NF-kappaB ligand (RANKL) and down-regulated osteoprotegerin (OPG) mRNA expression in PDL cells. The addition of cell-permeable PKI, an inhibitor of the cAMP/PKA signaling pathway, to the cocultures 8 h after the IL-1alpha stimulation inhibited IL-1alpha-induced TRAP+ cell formation. IL-1alpha-induced TRAP+ cell formation was completely blocked by either NS398, a selective inhibitor of cyclooxygenase (COX)-2, or PD98059, a specific inhibitor of extracellular signal-regulated kinase (ERK). Pretreatment with NS398 and PD98059 also inhibited both the up-regulation of RANKL and the down-regulation of OPG expression by IL-1alpha in PDL cells. IL-1alpha activated ERK phosphorylation and PD98059 greatly inhibited both COX-2 mRNA expression and PGE(2) production induced by IL-1alpha in PDL cells. In contrast, NEMO binding domain (NBD) peptide, a specific inhibitor of NF-kappaB signaling, did not affect COX2, RANKL, or OPG mRNA expression induced by IL-1alpha. These results suggest that IL-1alpha stimulates osteoclast formation by increasing the expression level of RANKL versus OPG via ERK-dependent PGE2 production in PDL cells.
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PMID:IL-1-induced receptor activator of NF-kappa B ligand in human periodontal ligament cells involves ERK-dependent PGE2 production. 1578 Sep 52


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