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)

It seems to be generally agreed that periodontal disease is a local manifestation of a systemic immune response. Interleukin-1 (IL-1), which has multiple biologic activities, is detected in the gingival sulcus fluid of periodontitis sites. Recent investigations have revealed that IL-1 and tumor necrosis factor (TNF) are analogous to osteoclast activating factor and promote bone resorption. These findings have suggested the possibility that IL-1 and TNF may play a significant role in the initiation and development of periodontal disease. However, it remains to be determined whether these cytokines influence periodontal tissue breakdown in periodontitis. To elucidate the mechanisms of tissue breakdown in periodontitis, we examined cytokine production by human periodontitis gingival tissue. Twelve periodontitis patients were included in this study. Control subjects with healthy periodontium consisted of nine individuals. Gingival samples were biopsied from inflamed or healthy gingival tissues. Biopsy specimens were dissected into fragments 3 mm in diameter and plated onto 24 well culture plates with RPMI 1640 medium. IL-1 activity was measured by a growth inhibition assay using melanoma cell line A 375. An enzyme-linked immunosorbent assay (ELIZA) was used for measuring levels of human IL-1 alpha, IL-1 beta. TNF alpha activity was measured by a growth inhibition assay using cell line LM2D6. IL-1 activity was detected in significantly (p less than 0.001) higher levels in culture supernatants from gingival tissues in periodontitis (48.0 +/- 23.3 units/ml) than in control tissues (2.3 +/- 0.6 units/ml), however, levels of IL-1 activity were not associated with periodontal pocket depth or extent of alveolar bone resorption in periodontitis.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Study of cytokine production in inflamed human gingival tissues in periodontitis. Interleukin-1 (IL-1 alpha, beta) and tumor necrosis factor (TNF alpha)]. 248 32

Interleukin-6 (IL-6) is involved in the final differentiation of B cells into antibody-producing cells. Recent studies reveal that IL-6 plays an important role in inflammation. Histopathological studies showed that a large number of plasma cells in periodontitis is usually seen in the apical parts of cellular infiltrates beneath the periodontal connective tissues. This evidence suggests that IL-6 may play a critical role in the development of periodontitis. Therefore, we examined IL-6 production in the gingival tissues. Twelve periodontitis patients and five gingivitis patients were included in this study. Nine individuals with healthy periodontium acted as control subjects. Biopsy specimens were dissected into fragments 3 mm in diameter and plated onto 24-well culture plates with RPMI 1640 medium. IL-6 activity in the culture supernatants was measured by IgM production assay using the cell line SKW6-CL4. IL-6 activity was detected at significantly higher levels (P less than 0.001) in culture supernatants from the gingival tissues in periodontitis (23.2 +/- 14.4 units/ml) and gingivititis (12.5 +/- 3.4 units/ml) than in control tissues (2.3 +/- 1.2 units/ml). Subsequently, the relationship between IL-6 activity and clinical stages was examined. The IL-6 levels before initial preparation (23.2 +/- 14.4 units/ml) were significantly higher (P less than 0.001) than those after initial preparation (1.4 +/- 1.8 units/ml), but were not associated with either periodontal pocket depth or the extent of alveolar bone resorption in periodontitis.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Cytokine production in inflamed human gingival tissues--interleukin-6]. 248 46

The purpose of this study was to compare, using cell blot analysis, the association of gingival tissue mononuclear cells (GTMC) isolated from lesions displaying histories of early-onset periodontitis (EOP; typically B-lymphocyte dominated) and gingivitis (typically T-lymphocyte dominated) with the B-cell stimulating cytokine, interleukin (IL)-4, and the T-cell stimulating cytokine, IL-2. Eleven EOP patients and 11 age- and gender-similar gingivitis control (GC) subjects participated. Gingival tissue adjacent to the alveolar crest normally removed during surgery was digested in collagenase-containing media and GTMC were isolated by density gradient centrifugation. Cells were separated into four aliquots. One was left unstimulated; the remainder were stimulated for 2 hours with Porphyromonas gingivalis outer membrane protein, mitogen Concanavalin A, or common antigen tetanus toxoid. Cells then were centrifuged onto transfer membranes and incubated in RPMI 1640 media for 6 hours to allow absorption of secreted cytokine. Membranes were treated with monoclonal anti-IL-2 or anti-IL-4, followed by a biotin-conjugated second layer, streptavidin-alkaline phosphatase and nitro blue tetrazolium/5-bromo-4-chloro-indolyl-phosphate (NBT/BCIP) color development. A higher percentage of GTMC from EOP patients were IL-2+ when stimulated with P. gingivalis compared with GTMC from GC patients (20 +/- 2% vs. 12 +/- 2%, P < 0.003). A higher percentage of non-stimulated GTMC from EOP patients produced IL-4 than from GC (22 +/- 4% vs. 6 +/- 3%, P < 0.00007), as well as when stimulated with P. gingivalis (22 +/- 3% vs. 13 +/- 2%, P < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Gingival cell IL-2 and IL-4 in early-onset periodontitis. 799 15

Cigarette smoking is a major risk factor in the development and further progression of periodontitis. However, little is known regarding the pathogenesis of smoking-related periodontal diseases. The purpose of this study was to examine the effects of nicotine, alone and in combination with lipopolysaccharide (LPS), on monocyte secretion of bone-resorbing factors, PGE2 and IL-1 beta. Peripheral blood monocytes (PBM) were isolated by counterflow centrifugal elutriation from 15 healthy, non-smoking donors. PBM were incubated for 24 h in RPMI 1640 containing nicotine (0, 50 ng/ml, 1 microgram/ml, 10 micrograms/ml and 100 micrograms/ml) with or without 10 micrograms/ml Porphyromonas gingivalis LPS or Escherichia coli LPS. Culture supernatants were assayed for PGE2 and IL-1 beta by ELISA. None of the nicotine preparations resulted in significant PBM secretion of PGE2 and IL-1 beta above that of unstimulated cultures. However, PGE2 release was potentiated 1.7-fold by the combination of P. gingivalis LPS and 10 micrograms/ml nicotine relative to P. gingivalis LPS alone (p < 0.05, one-way ANOVA). Prostaglandin E2 release also was potentiated 3.5-fold by P. gingivalis LPS and 100 micrograms/ml nicotine relative to P. gingivalis LPS alone (p < 0.00001, one-way ANOVA) and 3.1-fold by E. coli LPS and 100 micrograms/ml nicotine relative to E. coli LPS alone (p < 0.00001, one-way ANOVA). IL-1 beta secretion was lower for either LPS plus 100 micrograms/ml nicotine relative to LPS alone, although not significantly. These data demonstrate upregulation of LPS-mediated monocyte secretion of PGE2 by nicotine and suggest a potential role for nicotine in periodontal disease pathogenesis.
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PMID:Nicotine effects on PGE2 and IL-1 beta release by LPS-treated human monocytes. 870 46

The pathogenesis of tobacco-related periodontal diseases is not well understood. The purpose of this study was therefore to investigate smokeless tobacco extract (ST) and nicotine effects on prostaglandin E2 (PGE2) and interleukin-1beta (IL-1beta) secretion by peripheral blood mononuclear cells (PBMC, consisting of monocytes and lymphocytes) and gingival mononuclear cells (GMC). Both peripheral blood and gingival tissue adjacent to the alveolar crest were taken from non-smoking adult periodontitis patients. Gingival tissue was treated with collagenase and deoxyribonuclease and GMC and PBMC were isolated by Ficoll-Hypaque centrifugation. GMC and PBMC (100,000 cells/200 microl) were cultured for 24 hours in supplemented RPMI 1640 alone (control), or in supplemented RPMI 1640 containing 1% ST, 100 microg/ml nicotine, 1 microg/ml Porphyromonas gingivalis LPS, or 1 microg/ml P. gingivalis LPS and either 100 microg/ml nicotine or 1% ST. Enzyme immunoassays were used to quantify PGE2 and IL-1beta. Treatments were compared by repeated measures ANOVA. 100 microg/ml nicotine (7-fold, p<0.02) and 1% ST (3.5-fold, p<0.004) significantly increased secretion of PGE2 by PBMC relative to control cultures. 100 microg/ml nicotine and 1% ST, however, had no effect on IL-1beta secretion by PBMC. Enhanced PGE2 secretion also was seen when PBMC were treated with P. gingivalis LPS+ 100 microg/ml nicotine relative to P. gingivalis LPS alone (p<0.007). In contrast, 100 microg/ml nicotine significantly downregulated IL-1beta secretion by GMC relative to medium alone (p<0.008) and had no effect on PGE2 secretion by GMC. These data indicate that while nicotine and ST can stimulate PBMC to secrete PGE2, they cannot activate further mononuclear cells extracted from gingiva, possibly due to maximal previous stimulation in the periodontitis lesion.
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PMID:Nicotine and smokeless tobacco effects on gingival and peripheral blood mononuclear cells. 954 95

The objective of this study was to use an in vivo model of periodontitis (mouse calvaria) to quantify the effects of local release of secreted human macrophage products, 17beta-estradiol (E2), and proinflammatory lipopolysaccharide (LPS) on histologic bone resorption. Human THP-1 monocytes (106) were converted to macrophage phenotype by 500 ng/ml phorbol 12-myristate- 13-acetate (PMA) and treated as follows: no stimulation or Escherichia coli LPS (10 microg/ml) alone or in combination with a physiologic dose of E2 (100 pg/ml) for 24 h in RPMI/10% FBS, washed extensively, then incubated for 24 h in serum-free media. Supernatant products were concentrated and incorporated into a 4% (w/v) methylcellulose gel. Separate gels were incorporated with the following: LPS (500 microg/animal) alone, high dose of E2 (10 ng/animal) alone, a combination of LPS + E2, or gel only (controls). Loaded or control gels were placed into a polylactic acid occlusive dome, inserted subcutaneously over the calvaria of mature ovariectomized ICR Swiss mice (8 mice x 7 groups x 2 times [5/14 days] = 112 animals), then calvaria were evaluated histologically. Macrophage stimulation with LPS alone, but not LPS in combination with E2, produced supernatants which upregulated osteoclast numbers in the suture area compared to gel controls at 5 days (p = 0.009). The addition of LPS directly to the local delivery gels significantly upregulated osteoclasts in endosteal surfaces compared to gel controls at 5 days (p = 0.024) and at 14 days (p = 0.025). The addition of E2 to LPS down-regulated resorption to a level not different from gel controls at 14 days. This in vivo model appears effective in studying inflammatory bone resorption, which may be inhibited by E2 directly or through its influence on secreted macrophage products.
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PMID:Effects of locally-delivered human macrophage products and estrogen on murine inflammatory bone resorption. 1200 79