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)

Localized and chronically-inflamed gingival tissues of adult periodontitis (AP) are generally characterized as a hyper-responsiveness of B lineage cells where increased numbers of plasma cells occur. It was previously shown that high numbers of IgG subclass antibody-secreting cells (e.g., IgG1 > IgG2 > IgG3 > or = IgG4) with significant numbers of IgA subclass antibody-producing cells were seen in enzymatically dissociated gingival mononuclear cells (GMC) from inflamed periodontal tissues. An interesting finding was that the frequency of IgA2 plasma cells was elevated in the severe stage of AP when compared with the moderate stage. IgM plasma cells were essentially not found in these tissues. To understand the cytokine involvement in these increased B cell responses in inflamed gingiva, GMC isolated from inflamed tissues of AP patients were examined for cytokine production, specifically for IL-2, IL-4, IL-5, and IL-6 at both the protein and mRNA levels, since these cytokines have been shown to be essential interleukins for the regulation of the B cell response. Freshly-isolated GMC and peripheral blood mononuclear cells (PBMC) from AP patients were initially examined for IL-6 production because of its essential role for the terminal differentiation of B cells to become Ig-producing plasma cells. High levels of IL-6 were produced by GMC but not by PBMC unless cells were stimulated with T cell mitogen. A similar findings was also obtained when levels of IL-6 specific mRNA were examined in GMC and PBMC.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Cytokines and periodontal disease: immunopathological role of interleukins for B cell responses in chronic inflamed gingival tissues. 831 62

A unique characteristic of the localized inflammatory tissue in the periodontium (e.g., adult periodontitis [AP]) is the accumulation of IgG (IgG1 > IgG2 > IgG3 > or = IgG4) followed by IgA plasma cells (IgA1 > IgA2). However, the exact molecular mechanisms contributing to these elevated B-cell responses at the local disease site are still unknown. Thus, this study has examined the production of cytokines of importance in B-cell responses, e.g., interleukin (IL)-2, IL-4, IL-5, and IL-6 by gingival mononuclear cells (GMC) isolated from patients in severe stages of AP. These cytokines were assessed at the protein and messenger (m)RNA levels to understand their importance for the observed increased B-cell responses present in these tissues. Among the four cytokines tested by respective cytokine-specific, polymerase chain reaction and dot-blot hybridization, high levels of IL-5- and IL-6-specific mRNA were noted in GMC freshly isolated from AP patients. On the other hand, specific message for IL-2 and IL-4 were not present. Further, the analysis of culture supernatants of GMC also revealed that cells from AP patients spontaneously produced IL-5 and IL-6 but not IL-2 and IL-4. In contrast, when peripheral blood mononuclear cells isolated from the same patients were examined for these cytokines, no detectable levels of mRNA or secreted cytokines were noted. These results showed that GMC from localized inflammatory tissues in severe stages of AP possess a distinct cytokine profile represented by high levels of IL-5 and IL-6 mRNA expression and protein synthesis, whereas IL-2 and IL-4 were not detected. Further, this study supports the concept that AP is a localized inflammatory disease, because GMC from the inflamed tissue actively produce IL-5 and IL-6, whereas peripheral blood mononuclear cells from the same patients do not.
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PMID:Gingival mononuclear cells from chronic inflammatory periodontal tissues produce interleukin (IL)-5 and IL-6 but not IL-2 and IL-4. 847 96

Elevated numbers of plasma cells are associated with localized and chronically inflamed gingiva of patients with adult periodontitis. However, only limited information is currently available as to how cytokines produced by CD4(+) T cells are involved in these increased B cell responses in affected gingival tissues. When gingival mononuclear cells (GMC) were isolated from inflamed tissues and examined by flow cytometry, approximately 20-30% of lymphocytes were CD4(+) T cells. For the analysis of Th1 and Th2 cytokine expression by these CD4(+) T cells, RNA was extracted and reverse transcriptase-polymerase chain reaction (RT-PCR) was performed by using specific 5' and 3' primers for interferon-gamma (IFN-gamma) and IL-2 (Th1), IL-4, IL-5, IL-6, IL-10 and IL-13 (Th2) and beta-actin (internal control). Two distinct cytokine profiles were noted based on the expression of selected Th1 and Th2 cytokines, where one pattern was represented by expression of mRNA for IFN-gamma, IL-6, IL-10 and IL-13, while the second consisted of mRNA for IFN-gamma, IL-6 and IL-13. In most samples, mRNA for IL-2, IL-4 and IL-5 were not detected by cytokine-specific RT-PCR. When RNA was isolated from CD4(+) T cells of concanavalin A-stimulated peripheral blood mononuclear cells (PBMC) of the same patients and examined by RT-PCR, mRNA for all Th1 and Th2 cytokines were detected. These findings suggest that although human CD4(+) T cells are capable of producing an array of Th1- and Th2-type cytokines, the CD4(+) T cells associated with periodontitis are limited to production of IFN-gamma, IL-6, IL-13 and is some instances IL-10. CD4(+) T cells from diseased periodontal tissues are divisible into two groups based upon whether or not IL-10 is produced, together with IFN-gamma, IL-6 and IL-13.
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PMID:Selected Th1 and Th2 cytokine mRNA expression by CD4(+) T cells isolated from inflamed human gingival tissues. 860 41

Expression of mRNA for IL-1 alpha, IL-1 beta, IL-2, IL-4, IL-5, IL-6 and TNF-alpha in inflamed gingiva was quantitatively examined by ribonuclease protection assay and in situ hybridization. The IL-1 beta mRNA expression level was statistically high (P < 0.05) in periodontitis-affected tissues compared with that in gingivitis-affected tissues. The densities of macrophages (identified as CD68-positive cells) and CD45RO-positive cells infiltrating in the inflamed gingiva correlated statistically with IL-1 beta transcript levels (macrophages, P < 0.001; CD45RO-positive cells, P < 0.002). In situ hybridization revealed IL-1 beta mRNA expression in infiltrating cells, presumed to be macrophages. The IL-1 alpha and IL-6 mRNA expression levels were much lower than the IL-1 beta transcript level, and mRNAs for IL-2, IL-4, IL-5 and TNF-alpha were negligible in these gingival tissues. The results indicate that IL-1 beta is a cytokine expressed predominantly in inflamed gingiva and reflects the density of infiltrating macrophages and other leukocytes.
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PMID:IL-1 beta mRNA as the predominant inflammatory cytokine transcript: correlation with inflammatory cell infiltration into human gingiva. 883 19

It has been suggested that the types of inflammatory round cell infiltrates and the divergence in the cytokine production profile by macrophages and helper T cells regulate the course of infectious or inflammatory diseases, including periodontitis and gingivitis. We examined the expression of IL-1alpha, IL-1beta, IL-2, IL-4, IL-5, IL-6 and tumour necrosis factor-alpha (TNF-alpha) mRNA in the inflamed gingiva by in situ hybridization. The results of single-cell analysis were used as data sets for statistical analyses. The density of cells expressing IL-1alpha, IL-4 and IL-5 mRNA was higher in periodontitis than in gingivitis. IL-2 mRNA-expressing cells were almost absent in gingivitis specimens. Principal component analysis disclosed three factors explaining 84.8% of the variance: one accounting for 40.5% of the variance and mainly regulated by IL-1alpha, IL-1beta, IL-6 and TNF-alpha, and two others, explaining 29.9% and 14.4% of the variance, describing the relationship between the types of cytokines derived from macrophages or Th2 type. These results suggest that the cytokines produced by inflammatory cells infiltrating in the gingival tissue are influential on the progression of gingivitis, an acute and reversible inflammatory condition, to chronic and destructive periodontitis. Thus, periodontal disease progression may be regulated by the local cytokine network, and the bias in this network towards a Th2-type cytokine dominance could be an exacerbating factor.
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PMID:Relevance of local Th2-type cytokine mRNA expression in immunocompetent infiltrates in inflamed gingival tissue to periodontal diseases. 901 Feb 72

An accumulation of elevated numbers of macrophages (M phi) and Ig producing cells is associated with localized and chronically inflamed gingiva of patients with adult periodontitis. When gingival lymphocytes were isolated from inflamed tissues and examined by flow cytometry, approximately 20-30% of lymphocytes were CD4+ T cells. For the analysis of Th1 and Th2 cytokine expression by these CD4+ T cells, RNA was extracted and reverse transcriptase polymerase chain reaction (RT-PCR) was performed by using specific 5' and 3' primers for IFN-gamma and IL-2 (Th1), IL-4, IL-5, IL-6, IL-10 and IL-13, (Th2) and beta-actin (housekeeping gene). Two distinct cytokine profiles were noted based on the expression of selected Th1 and Th2 cytokines. Thus, one pattern was represented by the expression of mRNA for IFN-gamma, IL-6, IL-10 and IL-13, while the other case consisted of mRNA for IFN-gamma, IL-6, and IL-13. Except for a few cases, messages for IL-2, IL-4 and IL-5 were not detected by cytokine-specific RT-PCR. The predominant expression of Th2 cytokines (e.g. IL-6, IL-10 and IL-13) may contribute to the induction of high B cell responses in local disease sites. On the other hand, lack of IL-4 may be responsible for the accumulation of M phi in diseased periodontium. We also investigated whether a relationship exists between IL-4 receptor (IL-4R) expression and M phi persistence in the absence of exogenous IL-4. Gingival M phi, when compared with monocytes (MN)/M phi from peripheral blood mononuclear cells (PBMC), expressed high levels of IL-4R mRNA. When gingival M phi were incubated with recombinant IL-4 (rIL-4), the cell viability was dramatically reduced by apoptosis. These findings clearly show that the lack of IL-4 may contribute to the persistent occurrence of M phi at the disease site and addition of exogenous rIL-4 to gingival M phi cultures leads to cell death by apoptosis.
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PMID:Molecular and cellular mechanisms for periodontal diseases: role of Th1 and Th2 type cytokines in induction of mucosal inflammation. 908 20

In recent years advances in clinical techniques and procedures such as guided tissue regeneration and implants, have dominated periodontics. However, as we move towards the 21st century, emphasis is swinging 'back to basics' with the recognition that patient susceptibility to periodontal disease determines the ultimate outcome not only of the disease process but also of the treatment undertaken. In this context attention is returning to the host response and with the advent of clonal and molecular biological techniques, new insights are being gained into the nature of host susceptibility. Previous studies have suggested that a T-cell/macrophage immunoregulatory imbalance may exist locally in the periodontitis lesion and that this imbalance may be antigen specific. More recently, T-cell subsets have been dichotomized on the basis of their cytokine profiles. In general, Th1 cells produce IL-2 and IFN-gamma while Th2 cells produce IL-4, IL-5 and IL-6. The major function of Th1 cells is to mediate delayed type hypersensitivity. In contrast the major function of Th2 cells is to provide B-cell help. A model for periodontal disease has now been developed based on this functional dichotomy which provides a framework for the study of cytokine profiles in periodontal disease. Early studies in this context have demonstrated higher proportions of IL-4 and IL-13 producing cells in periodontitis tissues together with possible variations in IL-10 production. Clonal studies have shown that the selection of a particular cytokine profile is not antigen dependent and that differences may be due to the host susceptibility although this remains to be determined.
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PMID:Periodontics into the 21st century. 917 77

There is growing evidence for an important role of the immune system in the pathogenesis of periodontitis. To further characterize the possible immunoregulatory dysfunction of peripheral blood mononuclear cells (PBMC) in periodontitis patients, we investigated functional aspects of PBMC from patients with early-onset periodontitis (EOP) and adult periodontitis (AP). Compared to controls, we observed decreased proliferative responses of PBMC from patients with EOP following stimulation with a mitogenic stimulus (phytohemagglutinin). To investigate whether this abnormality reflects a modulation in cytokine production, we measured the in vitro production of interleukin (IL)-3, IL-5, granulocyte macrophage colony-stimulating factor (GM-CSF), and interferon-gamma (IFN-gamma) by activated PBMC. PBMC in EOP patients expressed significantly decreased levels of IFN-gamma protein in response to mitogenic stimulation. Reduced IFN-gamma secretion was associated with decreased IFN-gamma and IL-2 mRNA expression in these cells, as well as decreased HLA-DR surface expression on monocytes. On the other hand, we observed significantly higher levels of IL-5 and GM-CSF in the same system using PBMC from AP patients. These were comparable to the levels observed for patients with allergic asthma. These data imply that EOP is associated with decreased Th1-like cytokine expression, and that the PBMC response from patients with AP is predominantly Th2/Th0 in nature.
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PMID:Early-onset and adult periodontitis associated with abnormal cytokine production by activated T lymphocytes. 980 7

The aims of this study were to investigate the expression of pro-inflammatory, anti-inflammatory and immune-related cytokines present in periapical lesions. We investigated the expression of cytokines: namely interleukins IL-2, IL-4, IL-6, IL-10 and interferon-gamma (IFN-gamma) in formalin-fixed, paraffin-embedded sections of periapical granulation tissue. The study samples were biopsies from 24 patients with periapical lesions: 12 with periapical granulomas and 12 patients with radicular cysts. Immunohistochemistry was also performed on tonsillar tissue which served as a control. We utilised a set of specific monoclonal antibodies and polyclonal monospecific antibodies to detect cells that expressed the different cytokines within the tissues. We also considered the nature of the periapical immune response by investigation of the T-helper 1 (Th-1) and T-helper 2 (Th-2) lymphocyte subsets using their cytokine profile, i.e., Th-1: IL-2 and IFN-gamma and Th-2: IL-4, IL-5 and IL-6. Only a few cells were weakly positive for the IL-2 protein in each of the tissue sections. Cells that expressed IL-4 or IL-6 were far more numerous than cells that expressed either IL-2 or IFN-gamma. Thus, we demonstrated a greater number of Th-2 cells in periapical lesions. This relative ratio of the T-cell subsets underlines the importance of the anti-inflammatory mechanisms taking place in the diseased tissue manifested by the wide array of IL-10-expressing cells: B cells, T suppressor cells (CD8 (+)) and tissue macrophages. The numbers of inflammatory cells expressing the anti-inflammatory molecules far outnumbered the cells that expressed pro-inflammatory cytokines. Thus, the downregulation of the inflammatory response and the predominant Th-2 or humoral immune response in periapical periodontitis may be important features that dictate the outcome of the disease process in the periapical lesion.
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PMID:Cytokine expression in periapical granulation tissue as assessed by immunohistochemistry. 1087 89

Periodontal disease is an infection in which destruction occurs at sites remote from the infection, resulting in pathological pocketing. Intervening between the infection and the destruction is a dense mononuclear inflammatory infiltrate. It has been suggested that this infiltrate might have characteristics and the destructive potential of Th1-type T lymphocytes. To ascertain the nature of the infiltrates we investigated the expression of mRNA for IL-2, IL-5, and IFN-gamma by gingival mononuclear cells (GMC) from healthy (n = 8) or adult periodontitis (AP) patients (n = 25) by using cytokine-specific reverse-transcription/polymerase-chain-reaction (RT-PCR). GMC, as obtained from patients' tissues, expressed IL-2, IFN-gamma, or IL-5 mRNA. Significantly higher proportions of GMC from AP patients expressed IL-2 and IFN-gamma mRNA than did those from healthy subjects. IFN-gamma was the most consistent cytokine message detected. In other experiments, gingival T-lymphocytes (n = 12) and CD4+ and CD8+ gingival T-lymphocytes (n = 16) were isolated from gingival tissues removed surgically from AP patients. AP gingival T-lymphocytes expressed mRNA for IL-2, IFN-gamma, or IL-6 prior to stimulation. After stimulation with Con A, the cells significantly up-regulated IL-5 and IL-6 message expression. Both CD4+ and CD8+ gingival T-lymphocytes expressed IFN-gamma, IL-5, and some IL-2. This cumulative cytokine profile observed in these experiments is consistent with the predominance of Th1-type cells in pathological tissues and with Th2-type cells, which can also be present, being up-regulated under appropriate stimulation. Importantly, CD4+ and CD8+ lymphocytes were shown to express T1- and T2-type cytokine message, emphasizing the potential for CD8+ T-lymphocytes to participate in periodontal disease pathology.
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PMID:Cytokine profiles of T-lymphocytes from gingival tissues with pathological pocketing. 1102 73


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