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)

Interleukin-1(IL-1), a cytokine present in the gingiva and crevicular fluid of patients with periodontitis and in the periodontal ligament (PDL) of experimentally moved teeth, has multiple biological activities, including the ability to elicit bone resorption. Interleukin-6, also found in the gingiva of patients with periodontitis, may induce osteoclastic bone resorption through an effect on osteoclastogenesis. Here IL-6 production and its gene expression in response to recombinant IL-1 beta were examined in primary cultures of PDL cells. IL-1 beta stimulated IL-6 production by these cells in a dose- and time-dependent manner; this increase in IL-6 production was much higher than that in human gingival fibroblasts. In situ hybridization, using a synthetic oligonucleotide DNA probe of the IL-6 gene, revealed that most PDL cells expressed IL-6 mRNA in response to IL-1 beta treatment. The finding that IL-6 is produced by PDL cells and is regulated by IL-1 beta has revealed a potentially important mechanism for controlling alveolar bone resorption.
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PMID:Stimulation by interleukin-1 of interleukin-6 production by human periodontal ligament cells. 141 23

Cells expressing messenger RNA (mRNA) for inflammatory cytokines [interleukin-1 (IL-1), tumour necrosis factor-alpha (TNF-alpha), IL-6, IL-8] were demonstrated by in situ hybridization in human inflamed gingiva. When this technique was used in conjunction with immunohistochemistry, IL-1 alpha and/or beta and IL-8 messages were observed predominantly on macrophages infiltrating the gingiva. TNF-alpha messages were abundant on macrophages and T cells. In contrast, the IL-6 mRNA were more widely distributed on many types of cells such as macrophages, T cells, fibroblasts, endothelial cells and B cells. This study clearly identified the cells which express mRNA for inflammatory cytokines in inflamed gingiva and suggested an involvement of cytokine network in the generation of human periodontitis.
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PMID:Detection of inflammatory cytokine messenger RNA (mRNA)-expressing cells in human inflamed gingiva by combined in situ hybridization and immunohistochemistry. 162 99

It is well established that increased numbers of plasma cells occur in the localized tissues of chronic inflammatory diseases such as adult periodontitis, and enzymatic isolation has shown that most B lineage cells produce IgG-subclass with some IgA-subclass responses. It would be of importance to determine if excess production of cytokines in the localized lesion account for these responses and in the present study we have assessed gingival mononuclear cell (GMC) supernatants for cytokines that activate B cells including IL-6R expression and for levels of IL-6 present. Inasmuch as limited numbers (approximately 1 to 3 x 10(6) cells) of GMC were obtained from surgically removed tissues (approximately 400 mg), we have focused on the analysis of IL-6 production by GMC in this study. Further, initial evidence of additional cytokines that are produced by GMC and induce expression of IL-6R on resting B cells has been obtained. The GMC and PBMC from individual patients were cultured in the presence (or absence) of Con A. Higher levels of IL-6 were produced spontaneously by GMC when compared with Con A-stimulated PBMC. When PBMC cultures were supplemented with GMC supernatants obtained from the same patient, high numbers of spot-forming cells (SFC), mainly of IgG followed by IgA isotype, were seen. The induction of SFC by GMC supernatants was inhibited by incubation with a goat anti-human IL-6 antibody. When the effect of GMC supernatants on subclasses of PBMC SFC was determined, the response was IgG1 greater than IgG2 greater than IgG3 = IgG4 and IgA1 greater than IgA2, a pattern remarkably similar to the distribution of plasma cells in the GMC itself. To assess for cytokines in GMC supernatants that mediated B cell activation, supernatants containing anti-IL-6 were cultured with PBMC or purified B cells for 72 h. This treatment induced small proliferative B cell responses and elevated expression of IL-6R on B cells, but did not induce SFC responses. Further, incubation of B cells with GMC supernatants induced resting B cells (G0/G1) to enter the cell cycle (S and G2/M). Addition of human rIL-6 to these cultures on day 3 restored IgG- and IgA-subclass SFC responses by day 7. Cytokine-induced IL-6R expression also occurred in vivo because freshly isolated GMC expressed high levels of this receptor.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Cytokine regulation of localized inflammation. Induction of activated B cells and IL-6-mediated polyclonal IgG and IgA synthesis in inflamed human gingiva. 200 80

Extensive clinical, microbiological, hematological, and immunological studies were performed on a patient with early onset periodontitis (EOP) and two other members of the family. The proband, a 27-year-old female, had early onset periodontitis and a high level of serum rheumatoid factors (RF) with no diagnosable medical disease. Her mother had lost all her teeth at the age of 50 because of advanced periodontitis, while her elder sister was unaffected by periodontitis. Neither the proband's periodontally-affected mother nor her unaffected sister exhibited a detectable level of RF. In this study, we examined: 1) serum immunoglobulin G (IgG) antibody titers against putative periodontal pathogenic bacteria; 2) peripheral neutrophil functions; 3) phenotypic analyses of peripheral lymphocyte subpopulations; and 4) peripheral lymphocyte functions (T cell proliferative activity, ability of cytokine [interleukin (IL)-2, tumor necrosis factor-alpha, interferon-gamma, IL-6 and IL-8] and IgG and IgM productivity). High antibody titers to Actinobacillus actinomycetemcomitans, Porphyromonas gingivalis, and Campylobacter rectus were detected in the sera of the proband, as were high serum antibody titers to P. gingivalis in the mother and to C. rectus in the unaffected sister compared to the non-periodontitis affected subjects. The proband also showed enhanced neutrophil chemotaxis; a high percentage of pan-B cells; and high productivity of IL-6, IgG, and IgM compared to individuals who were not periodontally affected. The mother showed slightly low helper/induced T cells (Th/i) suppressor/cytotoxic T cells (Ts/c) ratios due to the elevated count of Ts/c, and high IFN-gamma productivity compared to control subjects.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Clinical and laboratory studies on a patient with early onset periodontitis and her family members. A case report. 762 61

Periodontitis is a general term for disease categories, including juvenile periodontitis (JP), rapidly progressive periodontitis (RPP), and adult periodontitis (AP), which may or may not share a common etiology and pathogenesis. These disease categories are characterized by differences in progression of tissue destruction and differences in age group susceptibility, but not, to our knowledge, by differences in cytokine responses of inflammatory cells. The present study examined blood cell counts and interindividual variation in the ability of PBMC of patients in three different categories of periodontitis to produce cytokines after stimulation with different oral bacterial species in vitro. The AP group had a significantly lower production of IL-1ra when stimulated with Porphyromonas gingivalis (P.g.) and Actinobacillus actinomycetemcomitans (A.a.) (P < 0.05). Streptococcus sanguis (S.s.), which is associated with normal periodontal conditions, induced extremely high levels of IL-1 alpha and TNF alpha production in all groups. The RPP group had a significantly higher number of monocytes (MC) than the AP group (P < 0.05). Additionally, JP patients had a significantly higher concentration of polymorphonuclear granulocytes compared to juvenile controls (P < 0.05). In conclusion, IL-1 alpha, TNF alpha, or IL-6 production by peripheral blood MC after in vitro stimulation with oral bacterial type stains may not distinguish different categories of periodontitis. The results support the hypothesis that the cytokine IL-1ra is produced in different concentrations in the two groups: RPP and AP. Furthermore, elevated MC concentration in the RPP group compared to the AP group may be an important pathogenic feature in RPP.
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PMID:Bacterial-stimulated cytokine production of peripheral mononuclear cells from patients of various periodontitis categories. 773 Sep 65

IL-4- and IL-6-producing cells in human periodontal disease tissues were investigated using immunohistochemical and in situ hybridization techniques. Immunohistochemical analysis demonstrated the presence of IL-4-producing cells within the CD45RO+ subset and the percentage of IL-4+ cells was significantly higher in periodontal lesions than in gingivitis tissues (p < 0.01). The percentage of IL-6-producing memory cells was higher in periodontal lesions compared with gingivitis tissues, although it was not statistically significant (p > 0.05). A reverse tendency in IL-4- and IL-6-positive cells was observed in a few individual cases. No IL-4 mRNA could be detected using the in situ hybridization technique. However, high levels of IL-6 mRNA were present in clinically healthy tissues, with a further increase in both epithelium and connective tissues affected by gingivitis, although only the former was significant (p < 0.025). There was a significant decrease in IL-6 mRNA in both the connective tissue (p < 0.025) and epithelium (p < 0.01) in periodontitis tissues compared with levels in gingivitis tissues. However, the levels of IL-6 mRNA in periodontal tissues were high compared with those of IL-1 mRNA, which was used in this study as a positive control. These results suggest that Th2-type cells may accumulate in periodontal lesions.
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PMID:IL-4- and IL-6-producing cells in human periodontal disease tissue. 781 73

IL-2, interferon-gamma (IFN-gamma), IL-4 and IL-6 producing T cells in periodontitis and gingivitis-affected human tissues were investigated by immunohistochemistry to clarify the relationship between T cell functional subsets and disease entity. Using alkaline-phosphatase anti-alkaline-phosphatase technique, the relative proportions of each cytokine-producing T cell were calculated in the crevicular 1/3, middle 1/3 and oral 1/3 areas selected in the connective tissue of sections. CD19:CD3 and CD4:CD8 ratios were determined on the serial sections. Compared with gingivitis tissues, the proportion of cytokine-producing cells in periodontitis-affected samples was higher overall in the crevicular 1/3 (P < 0.02). The middle 1/3 exhibited a higher percentage of cytokine-producing cells, except for IL-6-producing cells. Frequencies of cytokine-producing cells in the oral 1/3 did not differ. IL-4 was the prominent cytokine in periodontitis-affected tissues, with the highest proportion detected in the crevicular 1/3. The CD19:CD3 ratio was higher in periodontitis tissues irrespective of the location, indicating a B cell dominance in periodontitis lesions. Furthermore, a significant positive correlation between the proportion of IL-4-producing cells and the CD19:CD3 ratio was noted. The CD4:CD8 ratio consistently exceeded 2.0 in both periodontitis and gingivitis. These results suggest that immunoregulation of both periodontitis and gingivitis are T cell-dependent, but in periodontitis type 2 helper T cells predominate and thereby control B cell activation.
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PMID:Immunohistological analysis of T cell functional subsets in chronic inflammatory periodontal disease. 788 61

In this study, we sought to determine if human polymorphonuclear leukocytes (PMNs) derived from chronically inflamed tissues can produce inflammatory cytokines in vivo. Human gingival crevicular fluid (GCF) with adult periodontitis was collected, and PMNs in GCF were examined after purified by Ficoll-Hypaque gradient method. Cytokines from peripheral blood (PB) cells stimulated with concanavalin A, LPS, or zymosan were also characterized, since GCF contains predominantly PMNs (> 95%) with a small number of lymphocytes or macrophages. Production of interleukin-1 alpha (IL-1 alpha), IL-1 beta, tumor necrosis factor-alpha (TNF alpha), and IL-6 in GCF or culture supernatants of peripheral blood cells was determined by ELISA. Significant levels of IL-1 alpha and IL-1 beta secretion were found in GCF. PB cells in culture showed prominent cytokine production from monocytes/macrophages, followed by lymphocytes. Human peripheral blood PMNs (PB-PMNs) also produced low levels of IL-1 alpha and IL-1 beta, but not TNF alpha and IL-6. These cells were also examined for cytokine mRNA expression using the reverse transcription-polymerase chain reaction analysis. Highly purified PMNs (> 99.5%) from GCF expressed mRNA for IL-1 alpha, IL-1 beta and TNF alpha, but not for IL-6. PB-PMNs in culture also showed mRNA expression for IL-1 alpha, IL-1 beta, and TNF alpha in a time- and dose-dependent manner, especially after stimulation with zymosan. Therefore, we concluded that human PMNs from inflamed tissues can produce IL-1 alpha, IL-1 beta, and TNF alpha in vivo, but not IL-6.
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PMID:Human polymorphonuclear leukocytes derived from chronically inflamed tissue express inflammatory cytokines in vivo. 802 49

We have shown that gamma delta T cells in human gingiva have an intraepithelial location and, that in the chronic inflammatory disease periodontitis, the expression of CD45RO and CD8 or CD4 is induced on gamma delta T cells. To study the role of gamma delta T cells in local antibacterial responses, we determined the cytokine profiles of isolated human gingival cells. Different T cell subpopulations, isolated by positive selection with mAb-coated magnetic beads and macrophages, as well as epithelial cells, were analyzed for expression of mRNA for 15 cytokines by reverse transcriptase-PCR. The ultrastructure of gingival gamma delta T cells was also studied. The gamma delta T cells expressed mRNA for IFN-gamma, TNF-alpha, TGF-beta 1, and IL-6. Expression of IFN-gamma was a consequence of inflammation. CD4+ gamma delta T cells expressed IFN-gamma only, whereas CD8+ gamma delta T cells expressed all four cytokines. CD8+ cells expressing IFN-gamma, TNF-alpha, and IL-6 in combination suggest a cytotoxic effector function. Gingival gamma delta T cells contained cytoplasmic electron-dense membrane-bound granules and multivesicular bodies that are ultrastructural characteristics of cytotoxic cells. Epithelial cells from inflamed gingiva expressed HLA-DR, CD1a, CD1c, and heat shock protein 60 on the cell surface. They also expressed mRNA for IL-1 beta, IL-6, IL-8, TNF-alpha, and TGF-beta 1. Thus, epithelial cells may function as accessory cells in immune activation and, at the same time, be target cells for CD8+ gamma delta T cells reactive with CD1 Ag or heat shock protein. These results suggest that gamma delta T cells constitute a first line of defense in gingiva, preventing entrance of pathogens by cytotoxicity against infected and stressed epithelial cells, and by control of epithelial cell growth through secretion of regulatory cytokines.
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PMID:Cytokine profile and ultrastructure of intraepithelial gamma delta T cells in chronically inflamed human gingiva suggest a cytotoxic effector function. 805 26

Menopause and oophorectomy without estrogen therapy (ED) have been associated with increased production of bone-active cytokines by peripheral blood mononuclear cells. The current study extended evaluation to gingival crevicular fluid (GCF) levels of interleukin (IL)-1 beta and IL-6 in such subjects compared to premenopausal and postmenopausal estrogen-treated females (ES). 13 ED and 13 ES Caucasians with a history of moderate-severe adult periodontitis provided GCF from 1-3 clinically identical sites each (5-6 mm probing depth, 5-7 mm clinical attachment loss, bleeding on probing). 30 s GCF samples were obtained and evaluated for IL-1 beta and IL-6 levels using two-site enzyme-linked immunosorbent assays (ELISAs). The frequency of GCF IL-1 beta-positive subjects was elevated in ED versus ES (92% versus 23%; p < 0.0004, chi 2 analysis). IL-6 was detected more frequently in ED subjects (23% versus 8%; not significant); however, the frequency of IL-6 detection was low in both groups due to short sampling times. These data support the concept that clinical conditions causing low estrogen environments allow increased local production of the bone-active cytokine IL-1 beta, and perhaps IL-6.
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PMID:Gingival fluid IL-1 beta and IL-6 levels in menopause. 812 39


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