This study was carried out to examine the potency of the three surface components from Porphyromonas gingivalis to stimulate the murine macrophage cell line RAW264.7 to synthesize the pro-inflammatory cytokine tumor necrosis factor alpha(TNF-alpha) and nitric oxide (NO). Lipopolysaccharide(LPS), lipid A-associated proteins(LAP) and saline-extractable surface -associated material(SAM) were isolated from P. gingivalis 381. TNF-alpha release into culture supernatants was determined by two-site ELISA. NO production was assayed by measuring the accumulation of nitrite in culture supernatants. Western blot analysis of iNOS and analysis of reverse transcription(RT)-PCR products were carried out. The surface components extracted from this bacterium were almost equally potent in stimulating release of TNF-alpha and NO by RAW264.7 cells. TNF-alpha that was being measured immunologically was due to activation of TNF-alpha gene transcription. The present study clearly shows that P. gingivalis surface components fully induced iNOS expression in RAW264.7 cells in the absence of other stimuli. The ability of P. gingivalis surface components to promote the production of TNF-alpha and NO may be important in the pathogenesis of inflammatory periodontal disease.
Tumor Necrosis Factor-alpha

No abstract available.
Tumor Necrosis Factor-alpha*

Disease-modifying antirheumatic drugs (DMARDs) have been used for rheumatoid arthritis (RA) with the aim of controlling synovitis and reducing radiologic progression. Although methotrexate (MTX) is one of the most effective DMARDs, it may cause severe adverse effects. Especially, hematologic toxicity including leukopenia, thrombocytopenia, and fatal pancytopenia is reported in patients with impaired renal function, since renal excretion constitutes the major route of MTX elimination. Tumor necrosis factor-alpha (TNF alpha) inhibitors are well-established biologic agents for the treatment of RA and their clinical efficacy and safety are already demonstrated. But there were few reports on the efficacy and safety in dialysis patients. We described a case of hemodialysis patient with refractory RA that was successfully treated with etanercept, and discussed with literature review.
Tumor Necrosis Factor-alpha

To investigate effects of cytokines on rheumatoid synovial cells, proliferation and expression of cytokine and metalloproteinase genes were studied with the primary culture of rheumatoid synovial cells which was treated with TNF-alpha, GM-CSF, TGF-alpha, PDGF and IL-B. By [3H] thymidine incorporation assay, TGF-beta and PDGF increased proliferation of synovial cells by 1.5 and 2.5 folds respectively. Cytokine gene expression was assessed by RT-PCR. Rheumatoid synovial cells expressed constitutively TGF-beta and IL-B at a high level and IL-1B, GM-CSF, and MIP-1a at a relatively low level. TGF-beta, GM-CSF and PDGF increased IL-B expression. Expression of pro-inflammatory cytokines and chemokines was increased by GM-CSF and PDGF. Both GM-CSF and PDGF increased the expression of IL-1B, GM-CSF MIP-la and IL-8. In addition, GM-CSF enhanced expression of TNF-alpha. Stromelysin and collagenase are the major proteinases responsible for destruction ot joints in rheumatoid arthritis (RA). These genes were expressed constitutivefy in rheumatoid synovial cells. In summary, PDGF and GM-CSF may piay an important role by inducing or increasing expression of IL-1B, TGF-beta and PDGF by increasing proliferation of rheumatoid synovial cells.
Tumor Necrosis Factor-alpha

Present study aimed to investigate the immunological activities of cell wall associated protein antigen solubilized with Triton X-100 (TSP) from Mycobacterium tuberculosis H37Rv and conducted on 43 patients with pulmonary tuberculosis (newly diagnosed, medicated within 12 months and chronic refractory patients) and 17 normal healthy controls. These immunological responses were compared with those induced by the PPD or 30 kDa antigen from M, tuberculosis H37Rv culture filtrates, identified as biologically important secreted proteins. Proliferative responses to mycobacterial antigens were compared in peripheral blood mononuclear cells (PBMC) of healthy subjects and pulmonary tuberculosis patients. Signiticant blastogenic responses to the TSP were observed in healthy tuberculin reactors, newly diagnosed and some of antituberculosis drug-medicated patients by H-thymidine incorporation assay. IL-12 p40 and IFN-r mRNA expressions to the TSP were markedly increased, whereas IL-10 and TNF-a mRNA expressions were decreased at a 5 day-stimulation by PBMC in healthy tuberculin reactors, newly diagnosed and medicated patients. However, patients with chronic refractory tuberculosis exhibited more depressed IL-12 p40 and IFN-r mRNA expressions to all of the antigens than another groups. Interestingly, very low IL-10 and TNF-a mRNA expressions cultured with the TSP were also shown. These data suggest that the TSP may be involved in the macrophage activation by induction of Th1 stimulatory signals, such as IL-12, and suppression of Th1 inhibitory cytokine, IL-10.
Tumor Necrosis Factor-alpha

BACKGROUND: Histologically, vascular access stenosis is similar to the atherosclerotic lesion such as neointimal hyperplasia. However, the pathogenesis is not completely understood. The development of Inflammation and atherogenesis in hemodialysis population has been well recognized and is known as the malnutrition-inflammation-atherosclerosis (MIA) syndrome. We, therefore, examined the relationship between the vascular access stenosis and proinflammatory molecules in hemodialysis patients METHODS: Seventy-two regularly dialyzed patients were observed and the serum levels of the proinflammatory cytokines (IL-6, TNF-alpha and INF-gamma) were measured by ELISA. Patients were followed until the earliest date of death, modality change or loss to follow up. RESULTS: Vascular access stenosis was developed in thirty-five patients, and their mean duration of access survival was 22.7+/-37.6 months. In thirty-seven patients, vascular access remained patent during the study period (mean follow up; 70.9+/-46.6 months). In patients with autologous AV fistula, multivariate Cox regression analysis showed a significant contribution of INF-gamma to vascular access stenosis (Hazard ratio 1.024, p=0.044). In patients with AV graft, there was no significant relation between inflammatory cytokines and graft stenosis. There were positive correlations between the level of TNF-alpha and ferritin, and between transferrin and albumin. CRP and ferritin were negatively correlated with albumin and transferrin. CONCLUSIONS: Markers of inflammation were significantly associated with nutrition. And INF-gamma, one of the inflammatory cytokines, was related to the vascular access stenosis.
Tumor Necrosis Factor-alpha

BACKGROUND: Histologically, vascular access stenosis is similar to the atherosclerotic lesion such as neointimal hyperplasia. However, the pathogenesis is not completely understood. The development of Inflammation and atherogenesis in hemodialysis population has been well recognized and is known as the malnutrition-inflammation-atherosclerosis (MIA) syndrome. We, therefore, examined the relationship between the vascular access stenosis and proinflammatory molecules in hemodialysis patients METHODS: Seventy-two regularly dialyzed patients were observed and the serum levels of the proinflammatory cytokines (IL-6, TNF-alpha and INF-gamma) were measured by ELISA. Patients were followed until the earliest date of death, modality change or loss to follow up. RESULTS: Vascular access stenosis was developed in thirty-five patients, and their mean duration of access survival was 22.7+/-37.6 months. In thirty-seven patients, vascular access remained patent during the study period (mean follow up; 70.9+/-46.6 months). In patients with autologous AV fistula, multivariate Cox regression analysis showed a significant contribution of INF-gamma to vascular access stenosis (Hazard ratio 1.024, p=0.044). In patients with AV graft, there was no significant relation between inflammatory cytokines and graft stenosis. There were positive correlations between the level of TNF-alpha and ferritin, and between transferrin and albumin. CRP and ferritin were negatively correlated with albumin and transferrin. CONCLUSIONS: Markers of inflammation were significantly associated with nutrition. And INF-gamma, one of the inflammatory cytokines, was related to the vascular access stenosis.
Tumor Necrosis Factor-alpha

Tumor Necrosis Factor-alpha

In order to reveal immunopathogenesis of periodontal tissue destruction, it is important to clarify the molecular mechanism of trafficking and retention of activated leukocytes, including monocytes/macrophages. Gingival fibroblasts may be involved in the regulation of inflammatory cell accumulation in the extravascular periodontal connective tissues via cytokine production and surface expression of adhesion molecules. In this study, it was investigated the molecular basis for the adhesive interactions between monocytes and fibroblasts such as periodontal ligament fibroblast(PDLF), human gingival fibroblast(HGF), and human dermal fibroblast(HDF). First, it was examined the evidence whether monocyte-fibroblast cell contact may cause signal transduction in fibroblasts. Being directly in contact with fixed human monocyte cell line THP-1, or U937, upregulation of IL-6 production, TNF-alpha mRNA expression and increased cell proliferation could be seen for fibroblasts. IL-6 production induced by monocyte-fibroblast coculture were further increased when fibroblasts had been pretreated with IFN-gamma or IL-1beta, and monocytes with LPS. Next, it was examined the expression of ICAM-1 which has been known to be involved in accumulation and activation of leukocytes in inflammatory diseases such as periodontitis. ICAM-1 was upregulated up to 10-fold on PDLF, HGF, and HDF by exposure to IFN-gamma or IL-1beta. Furthermore, anti-ICAM-1 monoclonal antibody clearly blocked coculture-induced IL-6 production by fibroblasts, suggesting that ICAM-1/beta2 integrin pathway is involved in periodontal fibroblast-monocyte interaction. Overall, these findings provide evidence that periodontal fibroblasts could be involved in the accumulation and retention of monocytes/macrophages in periodontal inflammatory lesion at least in part by ICAM-1 expression. In addition, periodontal fibroblast-monocyte interaction could cause activation signals in fibroblasts intracellularly which result in cytokine production and cell proliferation. Thus, periodontal fibroblasts are speculated to play an important role in immunoregulation and tissue destruction in chronic periodontal diseases by interaction with monocytes/macrophages.
Humans ; Tumor Necrosis Factor-alpha

There is considerable experimental evidence to indicate that tumor growth is dependent on angiogenesis. However, we do not understand how the angiogenic activity is initiated by a given tumor. There is a clear distinction between a stage without neovascularization, which correlates with a paucity of metastases, and a stage in which increasing neovascularization correlates with a rising rate of metastasis. The authors therefore asked whether the extent of angiogenesis in human prostatic carcinoma is correlated with the tumor grades or some growth factors. To investigate how tumor angiogenesis correlates with tumor aggressiveness, the authors counted microvessels within the various grades of invasive prostatic carcinomas of 44 patients and the nodular hyperplasias of 10 patients. Highlighting of the vessels by immunohistochemical staining for factor VIII-related antigen and assessment of the tumor aggressiveness by the degree of expression of some growth factors(transforming growth factor-alpha, and beta, epidermal growth factor), tumor necrosis factor-alpha and tumor grading(Gleason's score) were done. As a result, both microvessel counts and the expression of growth factors and tumor necrosis factor correlated with tumor grades. In conclusion, the number of microvessels per 200 X fields in the areas of most intense neovascularization in a prostatic carcinoma may be a predictor of the patient's prognosis. Therefore, assessment of tumor angiogenesis may prove valuable in selecting patients with prostatic carcinoma, especially small needle biopsy, for aggressive therapy.
Humans ; Tumor Necrosis Factor-alpha