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Objective To explore the function of soluble apoptosis inhibitive factor Fas (sFas) in pathogenesis of Graves ophthalmopathy (GO). Methods The subjects were enrolled in the Second Affiliated Hospital of Harbin Medical University from January 2014 to January 2017, and they were divided into three groups: GO accompanied with Graves disease (GD) group, GO without GD group and normal control group, with 30 patients in each group. Serum levels of sFas in three groups were investigated with enzyme-linked immunosorbent assay, and serum levels of freeing triiodothyronine (FT3), serum free thyroxine (FT4), thyrotrophin (TSH), thyroglobulin antibody (TGAb), thyroid peroxidase antibody (TPOAb) were measured by chemoluminescent technique, and compared. Results The serum level of sFas in GO accompanied with GD group was (0.76 ± 0.13)μg/L, which was higher than that in GO without GD group [(0.63 ± 0.08)μg/L] and normal control group [(0.52 ± 0.05)μg/L], and there was significant difference (P＜0.01). The serum level of sFas in GO without GD group and normal control group had significant difference (P＜0.05). The serum levels of FT3, FT4, TGAb, TPOAb in GO without GD group were lower than those in GO accompanied with GD group (P＜0.01).The serum level of TSH in GO without GD group was higher than that in GO accompanied with GD group (P＜0.01). The concentration of sFas were negatively correlated with FT3, FT4, TSH, TGAb and TPOAb (P > 0.05). Conclusions Abnormal serum concentration of sFas can be observed in patients with GD and GO which proves that sFas may play a role in the pathogenesis of GD and GO.
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Objective To investigate the correlation between serum sFas and sLOX-1 with occurrence and development of acute coronary syndrome (ACS).Methods A total of 52 patients definitely diagnosed ACS (ACS group) by coronary artery angiography (CAG) were enrolled,including 23 cases of unstable angina (UA group) and 29 cases of acute myocardial infarction (AMI group),and contemporaneous 58 cases of non-coronary arterial stenosis confirmed by CAG were selected as the control group (NC group).The serum levels of sFas and sLOX-1 were measured by enzyme linked immunosorbent assay.Results Compared with the NC group,the serum levels of sFas and sLOX-1 in the ACS group were increased,the serum levels of sFas and sLOX-1 in the AMI group and UA group were higher than those in the NC group,moreover which in the AMI group were higher than those in the UA group (P＜0.01).The serum sFas level in the ACS group was positively correlated with the sLOX-1 level (r=0.825,P=0.001),but both had no obvious correlation with the serum levels of CK-MB and cTnⅠ (P＞0.05).Conclusion High levels of serum sFas and sLOX-1 may be the risk factors of ACS.
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Objective To investigate the the expression of soluble Fas (sFas) in the placenta of pregnancy induced hypertension (PIH) patients after perinatal. Methods Expression of sFas were detected by Fluorescent MGB Probe Real-Time PCR in 34 severe PIH patients and 30 healthy pregnant women served as normal controls.Results Expression of placenta sFas in 34 patients were significantly higher than those in normal controls.Conclusion PIH patients' placenta had higher expressiom of sFas; Detection of sFas may be helpful to value PIH degrade and sFas would be become a indicative markers of cell proliferation and apoptosis during the perinatal period.
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may sever as an indicator for the progression of malignant melanoma.
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BACKGROUND/AIMS: Apoptosis via Fas/FasL system is thought to be involved in the development of hepatocyte death in viral hepatitis B. In chronic hepatitis C, sFas/sFasL system was reported to control liver injury induced by Fas/FasL mediated apoptosis. To determine the role of sFas/sFasL system in chronic hepatitis B, we analyzed serum sFas/sFasL in 58 HBV patients and 29 healthy controls. METHODS: HBV patients were categorized into two groups; normal ALT (40 IU/L). Serum sFas/sFasL levels in HBV patients were measured by ELISA and was compared with those in 29 healthy controls. Serum ALT levels, histological activity, and Fas/FasL expression of liver were compared. RESULTS: Chronic hepatitis B patients with elevated ALT had significantly higher serum sFas levels than those in healthy controls (P<0.01). Serum sFasL levels, however, were significantly lower than those in healthy controls (P<0.01). Patients with moderate to marked degree of inflammation and fibrosis had significantly higher serum sFas levels than those in healthy controls (P<0.05). Serum sFasL levels had no correlation with the hepatic histological activity. Serum sFas/sFasL levels also had no significant correlation with the Fas/FasL expression of liver. CONCLUSIONS: Serum sFas/sFasL levels play a possible role in the pathogenesis of chronic hepatitis B. These results suggest that serum sFas levels might serve as a marker for estimating the degree of hepatic histological activity.
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Adult , Female , Humans , Male , Middle Aged , fas Receptor/analysis , Fas Ligand Protein/analysis , Hepatitis B virus/isolation & purification , Hepatitis B, Chronic/diagnosisABSTRACT
OBJECTIVE: To determine whether levels of soluble Fas (sFas) are elevated in patients with systemic lupus erythematosus (SLE) and correlated with clinical disease activity. METHODS: Serum samples were obtained from 62 SLE patients and 39 normal controls. We measured sFas levels using an enzyme-linked immunosorbent assay. Disease activity variables including Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) were examined. RESULTS: The mean age of the patients was 32.1 years (range 13~60 years) and the mean disease duration was 3.0 years (range 0.2~10.0 years); 1 patient was male (1.6%). The median serum sFas concentration was 610.0 pg/ml for SLE patients and 292.9 pg/ml in controls. The serum sFas concentration was significantly higher in SLE patients than in controls (p or =8) and inactive (SLEDAI <8) SLE patients. CONCLUSION: These results suggest that sFas levels are elevated in SLE patients, but sFas does not reflect disease activity.
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Humans , Male , Antibodies , Complement System Proteins , Enzyme-Linked Immunosorbent Assay , Lupus Erythematosus, Systemic , ROC Curve , Sensitivity and SpecificityABSTRACT
PURPOSE: The aim of this study is to determine the soluble Fas (sFas) levels in both sera and aqueous humor in patients with uveitis and compare them to the uveitis severity. METHODS: We measured the sFas levels in both sera and aqueous humor (AH) of patients (n=40) with uveitis and non-uveitis controls (n=27). The patients with uveitis comprised 24 Behcet's disease, 6 panuveitis, 5 anterior uveitis, 2 lens induced uveitis, 1 Vogt-Koyanagi-Harada-disease, 1 sarcoidosis, and 1 retinal vasculitis. The severity of uveitis was determined by the Hogan's grading method (0~4 grade) at the time of sampling. RESULTS:The concentration of aqueous sFas in uveitis patients was significantly higher than that in nonuveitis controls, while there was no difference in the serum concentration of sFas between the two groups. In the paired samples of serum and AH, obtained simultaneously, the aqueous sFas levels were higher than serum Fas levels in patients with uveitis, whereas the non-uveitis controls displayed significantly lower sFas levels in AH than in the serum. The sFas levels in AH or serum were not different between Behcet's uveitis and non-Behcet's uveitis. However, in patients with Behcet's uveitis, circulating sFas strongly correlated with aqueous sFas, which was not so in those with non-Behcet's uveitis. Patients (n=29) with more active (grade> or =2) uveitis had significantly higher levels of aqueous sFas than those (n=11) with less active (grade<2) uveitis. After treatment with steroid and/or immunosuppressive agents, aqueous sFas levels were decreased in parallel with a reduction in the number of inflammatory cells in the anterior chamber. CONCLUSIONS: The levels of sFas were elevated in patients with uveitis and correlated well with uveitis severity.
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Humans , Anterior Chamber , Aqueous Humor , Immunosuppressive Agents , Panuveitis , Retinal Vasculitis , Sarcoidosis , Uveitis , Uveitis, AnteriorABSTRACT
Objective To evaluate the target killing effect and metastasis prevention effect of soluble Fas combined with PKC inhibitor on the growth of human colorectal carcinoma implant in nude mice. Methods Orthotopic implantation and metastasis model of human colorectal carcinoma was reproduced in nude mice. Tumor tissue of tumor cell line HR-8348 with positive expression of FasL was implanted to the colonic wall of nude mice. After one week of tumor growth, mice were randomly divided into four groups according to the different agents injected into the peritoneal cavity. Twelve mice were in each group. The mice in the combined treatment group (recombinant soluble Fas coupled with PKC inhibitor + 5-Fu) were injected intraperitoneally 100?l (3mg/ml) recombinant soluble Fas coupled with PKC inhibitor and 0.5 mg of 5-Fu. (On the day of 0, 4, 8, 12 and16). At the same time, a group of tumor bearing mice were given recombinant soluble Fas coupled with PKC inhibitor only, and another group with 5-Fu only, and in the control group only normal saline was given. One month after implantation, tumor weight, inhibition rate and the presence of metastasis were evaluated respectively after the mice were sacrificed. Results Compared with control group, the orthotopically implanted tumors were significantly reduced in weight in mice treated with 5-Fu, recombinant soluble Fas coupled with the PKC inhibitor, and combined treatment, with respective inhibited rates of 43.1%, 79.9%, and 86.3%. Liver metastasis was also inhibited with significant decrease in incidence in 5-Fu group, recombinant soluble Fas coupled with the PKC inhibitor, and combined group compared with that in control group (75.0% vs 36.4%, 16.7%, and 0%). The incidence of peritoneal metastasis was also decreased significantly in 5-Fu, recombinant soluble Fas coupled with PKC inhibitor, and combined treatment compared with that in control group (100% vs 45.5%, 16.7%, and 8.3%, P
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Objective To investigate the correlation of serum sFasL level with carotid arterial intima- media thickness(IMT) and some known markers of inflammation, nutritional status in uremic patients with cardiovascular disease(CVD). Methods 134 uremic patients on hemodialysis were divided into two groups, CVD group (n=103) and non-CVD group (n=31). The serum level of sFasL, C-reactive protein (CRP), IL-6, TNF-? and albumin were measured by enzyme-linked immunosorbent assays (ELISA). The expression of Fas and FasL in radial arterial endothelial cells were observed both by immuohistochemical stain and by reverse transcription- polymerase chain reaction (RT-PCR). The Carotid arterial IMTs were measured by Color doppler ultrasonography. Results Compared with the non-CVD group, CVD group showed significantly increased serum sFasL, CRP, IL-6, and TNF-?, and decreased serum albumin(P
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Objective To investigate the relationship between IL-18 and apoptosis in patients with SLE by using testing the changes of IL-18 and soluble Fas/soluble Fas ligand in sera from the patients.Methods 58 patients with SLE were divided into three groups according to their SLEDAI score;sera from 58 patients,and 30 normal controls were tested for IL-18 and sFas/sFasL using ELISA assay.Results The level of IL-18 and sFas in sera from SLE patients was significantly higher than that of normal controls(P0 05).Besides,the increased level of IL-18 was correlated well with the increased level of sFas (?=0 496,P0 5).Conclusion The increased level of IL-18 may result in the elevation of serum sFas/sFasL in patients with SLE.They may play important roles in the pathogenesis of SLE.
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BACKGROUND: Fas is a member of the tumor necrosis factor (TNF)/nerve growth factor (NGF) receptor family. Triggering of the Fas receptor pathway by its ligand results in apoptosis. Soluble Fas consists of the extracellular region of Fas receptor and it binds to Fas ligand to inhibit the Fas and Fas ligand induced apoptosis. Recently some evidence indicates that the Fas/Fas ligand system represents an important pathway responsible for the induction of apoptosis in bone marrow CD34+ cells of patients with aplastic anemia. METHODS: We measured serum soluble Fas levels in 27 patients with aplastic anemia at diagnosis using ELISA to define the status of soluble Fas in this disorder. RESULTS: Levels of serum soluble Fas in patients with aplastic anemia were lower com-pared with that of normal healthy controls. No difference was noted in the serum soluble Fas levels according to severity of disease. No correlation was found between serum soluble Fas levels and hematologic parameters at diagnosis such as neutrophil count, lymphocyte count, platelet count and corrected reticulocyte count. CONCLUSION: These results indicate that serum soluble Fas levels are decreased in patients with aplastic anemia. Further studies recruiting more patients and measuring Fas receptor on peripheral blood lymphocyte subsets and bone marrow CD34+ cells concomitantly may be helpful to determine pathophysiology of bone marrow failure.
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Humans , Anemia, Aplastic , fas Receptor , Apoptosis , Bone Marrow , Diagnosis , Enzyme-Linked Immunosorbent Assay , Fas Ligand Protein , Lymphocyte Count , Lymphocyte Subsets , Neutrophils , Platelet Count , Reticulocyte Count , Tumor Necrosis Factor-alphaABSTRACT
Objective:To investigate the role of soluble Fas ligand (sFasL) in the mechanism of immune escape and counterattack of colorectal cancer.Methods:ELISA was used to detect the level of sFasL in the sera of colorectal cancer patients and the supernatant of SW480. Transmission electron microscopy (TEM), flow cytometry (FCM) analysis and fluorescence microscopy were used to examine the apoptosis of Jurkat induced by the sera of colorectal cancer patients and the supernatant of SW480. The apoptosis was also studied after pretreatment of Jurkat by Fas blocking antibody ZB4. The supernatant of African green monkey cell line Vero was used as control.Results:The concentration of sFasL in sera of colorectal cancer patients was 12.21?1.14 ?g/L before treatment, the concentration decreased significantly after treatment(P
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Objective To assess the level of soluble Fas (sFas) and soluble Fas ligand (sFasL) in the sera of patients with systemic lupus erythematosus (SLE),rheumatoid arthritis (RA),multiple sclerosis (MS)and insulin dependent diabetes mellitus (IDDM).Method The level of sFas and sFasL was determined by a sandwich enzyme linked immunosorbent assay.Anti ssDNA (single stranded DNA) was detected by indirect enzyme linked immunosorbent assay.Results The level of sFas in patients with SLE,RA,IDDM and MS was significantly higher than that in healthy individuals.It was interesting that among these autoimmune diseases,the level of sFas in the sera of patients with SLE was dramatically higher than that of the other diseases.The high level of sFasL accompanied by sFas was found in the sera of SLE and RA patients.In the sera of patients with SLE,the anti ssDNA antibody always accompanied by high concentration of sFas and,by contrast,no anti ssDNA antibody was found in all the patients in whose sera no sFas was found.In patients with IDDM,the sFasL level of the serum was significantly lower than that of the serum of healthy donors.Conclusion Serum sFas level of patients with SLE,RA,MS and IDDM is higher than that of healthy individuals.These results indicate that the sFas level can be used as a marker of disease progress and relaxing after treatment with the medicine.It is also demonstrated that there is relationship between the level of anti ssDNA antibody and sFas.The level and significance of serum sFas and sFasL in these autoimmune disease patients are under investigation.
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Objective To investigate the influence of iodine on apoptosis of thyrocytes and to study the effect of iodine on the pathogenesis of thyroid diseases. Methods Normal human thyrocytes were cultured in the absence or presence of 10 -8 ～10 -4 mol/L NaI. Apoptosis, Fas expression, Bcl-2 and Bak expression and Fas and soluble Fas (sFas) mRNA levels in thyrocytes were detected by flowcytometry, Western blot and semi-quantitative reverse transcription polymerase chain reaction (RT-PCR) respectively, sFas was detected in supernatant of cultured thyrocytes by ELISA. Results (1) Low concentration of iodine (10 -8 mol/L) could inhibit apoptosis, while high concentrations of iodine (10 -6 ～10 -4 mol/L) increased apoptosis (P
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The Changes of soluble Fas levels in Patients with Autoimmune Thyroid Diseases BACKGROUD: Apoptosis was observed in thyroid tissue from Hashimoto disease but not those from Graves disease. Recently Fas and Fas ligand interactions among thyrocytes were suggested to development of clinical hypothyroidism in Hashimoto disease.Soluble Fas produced as the form lacking the tranmembrane domain due to alternative splicing, is supposed to inhibit Fas-Fas ligand interaction and blocks Fas mediated apoptosis. METHODS: In tbis study, we measured serum soluble Fas to determine the possible involvement of this molecule in the autoimmune thyroid disease by enzyme linked immunosorbant assay in 29 patients with Graves disease, 30 patients with Hashimotos disease and 19 normal controls. RESULTS: Compared with normal subjeets (4.26 +/- 1.00 U/mL), soluble Fas was not increased in patients with Graves disease (4.23 +/- 1.14 U/mL, p>0.05) but it was increased in throtoxic Graves patients (4.70 +/- 1.26 U/mL, p<0.05) compared to euthyroid Graves (3.72 +/- 0.73 U/mL, p<0.05) and normal subjects (4.26 +/- 1.00 U/mL, p<0.05). The euthyroid and hypothyroid patients with Hashimoto disease showed low soluble Fas levels, 2.94 +/- 0.54 U/mL and 2.74 U/mL, respectively compare to the patients with Graves disease and normal subjects. The thyroid hormone levels to (T3 T4 and free T4) showed positive correlation with the serum titers of antithyroid autoantibodies, antithyroglobuin antibodies, antiperoxidase antibodies and thyrotropin binding inhibitor immunoglobulins. CONCLUSION: We found that the patients with thyrotoxic Graves disease had increased level of serum soluble Fas and the patients with Hashimoto disease showed low levels of soluble Fas compared to normal controls. Increased soluble Fas in Graves disease suggests increased expression of alternatively spliced Fas mRNA variant and decreased soluble Fas in Hashimoto disease suggests decreased Fas mRNA variant and increased full length membrane Fas, so these findings are related to the promotion of apoptosis of thyroid cells during autoimmune reaction in Hashimotos disease.
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Humans , Alternative Splicing , Antibodies , Apoptosis , Autoantibodies , Fas Ligand Protein , Graves Disease , Hashimoto Disease , Hypothyroidism , Immunoglobulins , Membranes , RNA, Messenger , Thyroid Diseases , Thyroid Gland , ThyrotropinABSTRACT
To detect the soluble Fas (sFas) receptor level in sera from patients with myelodysplastic syndrome (MDS) and acute leukemia (AL), and investigate its clinical significance, the levels of sFas receptor in sera from 18 patients with MDS and 42 patients with AL were detected by using ELISA methods. The results suggested that the sFas receptor levels in sera from patients with MDS-RA were significantly lower than that from normal control (2.89?1.72 ng/ml vs 6.29?1.07 ng/ml, P
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0. 05 ]. However, the level of sFas was significantly higher in the patients with CHF than those of the cardiac function class Ⅰ group [CHF group: 1353. 30 ? 507. 71 (cardiac function class Ⅱ 1154. 85 ? 371.20, class Ⅲ 1412. 88 ? 493. 62, class Ⅳ 1875.67 ? 806. 10) vs. cardiac function class Ⅰ group:983. 11 ? 416.26 pg/ml, P