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Soluble Fas Ligand (soluble + fa_ligand)
Selected AbstractsMatrix metalloproteinase inhibitor reduces apoptosis induction of bone marrow cells in MDS-RAEUROPEAN JOURNAL OF HAEMATOLOGY, Issue 1 2004Kosei Arimura Abstract:,Background and objectives:,We examined the involvement of apoptosis with myelodysplastic syndrome (MDS) accompanied by peripheral cytopenias despite normo-hypercellular bone marrow. Materials and methods:,Bone marrow smears from 31 patients with MDS-refractory anemia (RA) and five normal controls were stained using the in situ end labeling (ISEL) method. Next, the inhibitory effects of a caspase-3 inhibitor, matrix metalloproteinase inhibitor (MMPI), anti-tumor necrosis factor (TNF)- , or anti-Fas antibody upon the apoptosis induction in overnight cultures of bone marrow cells from the patients were examined. Further, TNF- ,, transforming growth factor (TGF)- , and soluble Fas ligand (sFasL) concentrations in culture supernatants of the cells were assessed by enzyme-linked immunosorbent assay (ELISA). Results:,The incidence of ISEL-positive cells among MDS patients was significantly higher than in normal controls (50.8 ± 14.0% vs. 11.3 ± 2.4%; P < 0.0001). A caspase-3 inhibitor reduced significantly the ISEL-positive rates (32.6 ± 15.2% vs. 50.2 ± 16.5%; P < 0.0001). Anti-TNF- , or anti-Fas antibody reduced the ISEL-positive rates significantly (28.2 ± 6.0%, 29.2 ± 5.8%, vs. 44.2 ± 3.4%, P < 0.001, P = 0.001, respectively). KB-R7785 also significantly decreased the ISEL-positive rates (18.0 ± 9.3% vs. 43.6 ± 14.0%; P < 0.0001). The concentration of TNF- , was significantly reduced by KB-R7785 (P < 0.05), whereas that of TGF- , was not. Concentration of sFasL was under detectable level in the present assay system. The derivatives of KB-R7785 that can be administrated orally showed inhibitory effect on apoptosis induction as well. Conclusions:,These findings suggest that MMPIs inhibits the apoptosis induction of MDS bone marrow cells via the inhibition of TNF- , and probably sFasL secretion, and that MMPIs can be used to control the abnormal induction of apoptosis in MDS. [source] Plasma-soluble Fas (APO-1, CD95) and soluble Fas ligand in immune thrombocytopenic purpuraEUROPEAN JOURNAL OF HAEMATOLOGY, Issue 4 2000Chie Yoshimura Abstract: We investigated the levels of various cytokines and soluble factors in ITP patients, in order to determine the influence of these factors on the pathogenesis of ITP. We found increases in IL-2, IL-6, IFN-,, and M-CSF levels in ITP patients compared with those in healthy individuals. On lymphocyte phenotype analysis, we found no clear difference in total T cell population (CD2+ CD19, cells) or cytotoxic T cell frequency (CD8+ CD11b, cells) between these two groups. The frequency of helper/inducer T cells (CD4+ CD8, cells) was decreased in ITP patients. There was a significant increase in activated T cells (CD3+ HLA-DR+ cells) in ITP patients. Furthermore, frequencies of NK cells of potent activity (CD16+ CD56+ cells) were significantly elevated in ITP patients. Seventeen of the 54 ITP patients (31.5%) had elevated levels of sFas, and 11 of the 54 patients (20.4%) of sFasL. In addition, a significant increase of sFasL was observed in sFas-positive ITP patients, and in these patients the sFasL level was correlated with that of sFas (r=0.687, p<0.01). We found significant increases in IL-2 and sIL-2R levels in sFas-positive ITP patients. For other factors examined, however, there were no differences in level between sFas-positive and-negative ITP patients. Percentages of activated T cells (CD3+ and HLA-DR+ cells) and NK cells (CD16+ and CD56+ cells) were significantly higher in sFas-positive ITP patients than in sFas-negative ITP patients. These findings suggests that the pathogenesis of ITP includes alteration of the Fas/FasL pathway. [source] Evaluation of apoptosis in Epstein,Barr virus-associated hemophagocytic lymphohistiocytosis,JOURNAL OF MEDICAL VIROLOGY, Issue 3 2006Jun-ichi Kawada Abstract Epstein,Barr virus (EBV) is known to be a causative agent of hemophagocytic lymphohistiocytosis (HLH). To investigate association of apoptosis in the pathogenesis of EBV-associated HLH, the serum EBV loads, and serum concentrations of soluble tumor necrosis factor receptor 1 (sTNF-R1), soluble Fas ligand, and cytochrome c were examined in 15 patients with EBV-associated HLH and 24 patients with infectious mononucleosis (IM). Levels of sTNF-R1 are known to reflect the biological activity of TNF-, and cytochrome c is a specific marker of apoptosis. EBV loads, and concentrations of sTNF-R1 and cytochrome c were significantly higher in patients with EBV-associated HLH than in patients with IM. On the other hand, there were no statistically significant differences in the concentrations of soluble Fas ligand. In patients with EBV-associated HLH, EBV loads, concentrations of sTNF-R1, and cytochrome c were correlated with each other. These results suggest that apoptosis, which is dependent on the EBV load and could be mediated by TNF-,, plays a major role in the pathophysiology of EBV-associated HLH. J. Med. Virol. 78:400,407, 2006. © 2006 Wiley-Liss, Inc. [source] Variations in the serum concentrations of soluble Fas and soluble Fas ligand in Vietnamese patients infected with hepatitis B virusJOURNAL OF MEDICAL VIROLOGY, Issue 2 2004Le H. Song Abstract Earlier studies of both chronic hepatitis B and C virus (HBV and HCV) patients have shown a strong correlation between the soluble membrane Fas (sFas) and Fas protein expression on hepatocytes. The serum concentrations of sFas and soluble Fas ligand (sFasL) was examined in both healthy and HBV-infected Vietnamese patients to determine their relationship with the outcome of HBV infection. Patients with chronic rather than acute HBV had significantly higher amounts of sFas and sFasL, whilst the highest concentrations of both molecules were detected in those with malignant forms of HBV infection. sFas and sFasL concentrations tended to increase with a profile that paralleled the progression from asymptomatic to acute through chronic to malignant states, most markedly in the case of sFas. The sFas:sFasL ratio highlighted the relative predominance of sFas in those with acute and chronic HBV compared with asymptomatic or severe forms. In patients with hepatocellular carcinoma (HCC) a significant correlation was also observed between sFasL and alpha-feto protein (AFP) levels. The results indicate that sFas and to a lesser extent sFasL levels are to some degree associated with clinical progression in HBV infection. J. Med. Virol. 73:244,249, 2004. © 2004 Wiley-Liss, Inc. [source] Soluble Fas (sFas) and soluble Fas ligand (sFas-L) balance in laryngeal carcinoma before and after surgical treatmentJOURNAL OF SURGICAL ONCOLOGY, Issue 2 2003Lorenzo Pignataro MD Abstract Background and Objectives Fas and its specific ligand (Fas-L), both of which are involved in apoptosis, exist in membrane-bound and soluble forms. The soluble forms (sFas and sFas-L) have been observed in various tumours, but their clinical significance has not yet been clarified. The aim of this study was to assess serum sFas and sFas-L levels in patients with laryngeal squamous cell carcinoma (LSCC) and their possible correlations with surgical treatment. Methods Serum sFas and sFas-L levels were determined by ELISA in samples taken from 26 LSCC patients on the day before surgery (T0), and 2 weeks (T1) and 6 months after surgery (T2), and in samples taken from 35 healthy volunteers. Results The mean serum sFas levels in the 35 healthy volunteers and the 26 LSCC patients at T0 were respectively 5941,±,411 pg/ml and 6290,±,652 pg/ml (P,=,0.63), and the mean serum sFas-L levels were 0.1,±,0.05 ng/ml and 2.95,±,0.8 ng/ml (P,<,0.0001). After surgery, there was a statistically significant decrease in sFas at both T1 (P,<,0.05) and T2 (P,<,0.01), and in sFas-L at T2 (P,<,0.01). Conclusions The decrease in sFas and sFas-L levels after surgery suggest that they may be produced by or closely linked to tumour cells. Larger prospective clinical studies of patients with LSCC will be needed to establish the clinical significance of sFas and sFas-L, as reported for other neoplasms. J. Surg. Oncol. 2003;83:112,115. © 2003 Wiley-Liss, Inc. [source] Asperfuranone from Aspergillus nidulans Inhibits Proliferation of Human Non-Small Cell Lung Cancer A549 Cells via Blocking Cell Cycle Progression and Inducing ApoptosisBASIC AND CLINICAL PHARMACOLOGY & TOXICOLOGY, Issue 1 2010Clay C. C. Wang To identity the anti-cancer mechanism of asperfuranone, we assayed its effect on apoptosis, cell cycle distribution, and levels of p53, p21 Waf1/Cip1, Fas/APO-1 receptor and Fas ligand. Enzyme-linked immunosorbent assay showed that the G0/G1 phase arrest might be due to p53-dependent induction of p21 Waf1/Cip1. An enhancement in Fas/APO-1 and its two form ligands, membrane-bound Fas ligand (mFasL) and soluble Fas ligand (sFasL), might be responsible for the apoptotic effect induced by asperfuranone. Our study reports here for the first time that the induction of p53 and the activity of Fas/Fas ligand apoptotic system may participate in the anti-proliferative activity of asperfuranone in A549 cells. [source] ISOLIQUIRITIGENIN INHIBITS THE PROLIFERATION AND INDUCES THE APOPTOSIS OF HUMAN NON-SMALL CELL LUNG CANCER A549 CELLSCLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 7 2004Ya-Ling Hsu SUMMARY 1.,Isoliquiritigenin (ISL) is a natural pigment with the simple chalcone structure 4,2,,4,-trihydroxychalcone. In the present study, we report, for the first time, ISL-induced inhibition of the proliferation of the human non-small cell lung cancer A549 cell line. 2.,The results showed that ISL not only inhibited A549 cell proliferation, but also induced apoptosis and blocked cell cycle progression in the G1 phase. An ELISA assay demonstrated that ISL significantly increased the expression of p53 and p21/WAF1 protein, which caused cell cycle arrest. 3.,An enhancement in Fas and its two ligands, namely membrane-bound Fas ligand (mFasL) and soluble Fas ligand (sFasL), may be responsible for the apoptotic effect induced by ISL. 4.,Taken together, the results indicate that the p53 and Fas/FasL apoptotic system may participate in the antiproliferative activity of ISL in A549 cells. [source] Comparative Evaluation of Cytokines, T-Cell Apoptosis, and Costimulatory Molecule Expression in Tuberculous and Nontuberculous PleurisyCLINICAL AND TRANSLATIONAL SCIENCE, Issue 3 2008Priya Rajavelu M.Sc. Abstract In this study, we compared several immune parameters in tuberculosis (TB) and nontuberculosis (NTB) pleurisy to gain an understanding of the mechanism behind enhanced Th1 apoptosis that occurs at sites of active Myobacterium tuberculosis (M. tuberculosis) infection. An initial evaluation of the accumulated cytokines in pleural fluid (PF) demonstrated that both TB and NTB pleurisy were associated with prointflammatory cytokines, while only TB pleurisy had augmented expression of interferon (IFN)-, and soluble Fas ligand (sFASL). Despite enhanced expression of the apoptosis-inducing molecule in TB pleurisy, T cells derived from both types of pleurisy exhibited significant apoptosis. In both groups, T-cell apoptosis correlated with low expression of CD80 on PF-derived macrophages and elevated accumulation of TGF-, in the PF. A causative correlation between TGF-, and low CD80 expression in the two groups was established by in vitro studies demonstrating TGF-, inhibition of CD80 upregulation in a macrophage cell line. Together, the findings allude to the possibility that activation in the absence of appropriate CD80 costimulation is the mechanism that leads to T-cell apoptosis at sites of active M. tuberculosis infection. Furthermore, the findings also indicate that T-cell apoptosis is perhaps a host regulatory mechanism to limit inflammation, rather than a pathogen-induced immune deviation. [source] | ||||||||||