Cytotoxic T cell (CTL) covers several subtypes, which are CD8+, CD4 and CD4-CD8-. CTL derives from T cell repertoire in lymphoid hematopoietic stem cells. It matures in thymus and is activated in peripheral lymphoid tissues. Effector CTL kills the target cells by 2 ways. One is apoptotic effect mediated by FasL-Fas pathway and the other one is cytolytic effect mediated by granzymes. CTL has aroused great attention due to its significance in anti-tumor and anti-virus.
Animals ; Fas Ligand Protein ; Humans ; Membrane Glycoproteins ; immunology ; Perforin ; Pore Forming Cytotoxic Proteins ; T-Lymphocytes, Cytotoxic ; immunology ; fas Receptor ; immunology

OBJECTIVETo investigate the relationship of Fas mRNA and protein expression and apoptosis in human oral squamous cell carcinoma.

METHODSNorthern blot and flow cytometry (TUNEL method) were used to detect the expression of Fas mRNA and Fas protein, cell cycle and apoptotic level in oral squamous cell carcinoma. The relationship between Fas gene expression and OSCC apoptosis was analyzed statistically.

RESULTSFas mRNA and protein could be detected in all five normal oral mucosa specimens. There was positive correlation between expression of Fas mRNA/protein and cell differentiation as well as apoptosis in OSCC (P < 0.005).

CONCLUSIONThe expression of Fas gene was highly correlated with the differentiation and apoptosis in OSCC.

Apoptosis ; Carcinoma, Squamous Cell ; metabolism ; Humans ; Mouth Neoplasms ; metabolism ; fas Receptor ; metabolism

CD40 Ligand ; pharmacology ; HL-60 Cells ; drug effects ; Humans ; fas Receptor ; metabolism

OBJECTIVETo explore the role of superoxide dismutase (SOD) coenzyme in regulation of Fas/FasL signal transduction and apoptosis of alveolar macrophages in pneumoconiosis patients.

METHODS50 male and Han nationality cases, including the dust exposed workers, Phase I, II pneumoconiosis patients confirmed by local pneumoconiosis diagnosis group according to GBZ 70 - 2002 diagnosis standard, who underwent whole lung lavage treatment were chosen as subjects. Their alveolar macrophages (AMs) were collected and purified. The cells were divided into three groups: the untreated group, the Fas/FasL group and the SOD group. 5 x 10(6) purified AMs were added into incubating bottles containing DMEM for 2 hours for purifying, added with SOD coenzyme and other block reagents separately, and then incubated for 24 hours in CO(2) incubation. The cells were harvested and lysed. Western-blot were used to analyze the expressions of Fas, FasL, Caspases-8 and Caspases-3. Software of Quantity One 7.0 was used to analyze the relative quantity of Fas, FasL, Caspase-8 and Caspase-3. TUNEL and DNA fragment analysis were used to analyze AMs apoptosis.

RESULTSThe apoptosis index in SOD coenzyme group (9.50 +/- 2.76)% and Fas/FasL group (14.01 +/- 2.56)% was significantly lower than that of in untreated group (19.18 +/- 2.83)% (P < 0.05). The catachrestic DNA ladder appeared in untreated group, was looming in Fas/FasL group, and was not found in the SOD group. The expressions of Fas, FasL, Caspase-8 and Caspase-3 of phase I and II in SOD group were higher than in the other two groups (P < 0.05). There was no significant difference in the expression of Fas, FasL, Caspase-8 and Caspase-3 among different phases of pneumoconiosis (P > 0.05).

CONCLUSIONSOD coenzyme can effectively regulate Fas/FasL signal transduction and block AMs apoptosis.

Adult ; Apoptosis ; Cells, Cultured ; Fas Ligand Protein ; metabolism ; Humans ; Macrophages, Alveolar ; metabolism ; pathology ; Male ; Middle Aged ; Pneumoconiosis ; metabolism ; pathology ; Signal Transduction ; Superoxide Dismutase ; metabolism ; fas Receptor ; metabolism

OBJECTIVETo study the significance of Fas and Fas-L expression in adenocarcinoma of uterine cervix.

METHODSBoth carcinoma tissue and their surrounding tissues from 36 patients with adenocarcinoma of uterine cervix, previously untreated either by radiation or chemotherapy, were studied for the expression of Fas and Fas-L by immunohistochemical stain with DNA apoptosis fragment detected by TUNEL.

RESULTSThe TUNEL labeling index was negatively correlated with differentiation of adenocarcinoma of cervix. Compared to highly differentiated and moderately differentiated tumor, the TUNEL labeling index was reduced obviously in poorly differentiated adenocarcinoma (P < 0.01). Fas expression was detected in 31 cases (86%) while there were only 3 weakly stained in the normal endocervical glands around the carcinoma. The 5 unstained carcinomas were 3 highly differentiated and 2 moderately differentiated. The positively stained Fas was associated with differentiation; the stronger the stain, the less differentiation there was. The Fas-L expression was detected in all adenocarcinomas while there was only 1 weakly stained in the normal ones. No significant difference was found in the expression of Fas-L in carcinomas with different degrees of differentiation. No correlation was observed between Fas and Fas-L expression.

CONCLUSIONSThe Fas expression is positively correlated with the different degrees of differentiation and Fas-L expression may be associated with the escape from of immunal surveillance.

Adenocarcinoma ; diagnosis ; metabolism ; Apoptosis ; physiology ; Biomarkers, Tumor ; biosynthesis ; Cell Differentiation ; physiology ; Fas Ligand Protein ; Female ; Humans ; Immunohistochemistry ; Membrane Glycoproteins ; biosynthesis ; Uterine Cervical Neoplasms ; diagnosis ; metabolism ; fas Receptor ; biosynthesis

OBJECTIVETo investigate the effects of FAS and FASL gene polymorphisms on genetic susceptibility of coal worker's pneumoconiosis and their relationship to the pulmonary fibrosis.

METHODS340 with coal worker's pneumoconiosis (CWP) and 312 coal mine workers (controls) exposed to the coal dusts were selected. FAS-1377G > A, FAS-670A > G and FASL-844T > C gene polymorphisms were analyzed by PCR-RFLP techniques.

RESULTSThe distribution frequencies of genotypes of FAS-1377, FAS-670, FASL-844 genotypes in CWP had no significant differences compared to the control. Compared to CWP patients with exposure year > or = 25, the risk of pneumoconiosis with FAS-1377 GA/AA genotype was significantly higher than those with FAS-1377GG in the patients working age < 25 years (P = 0.098, 95% CI: 0.932 approximately 2.298); the risk of CWP in those with FAS-670AG genotype was higher than those with FAS-670GG genotype (P = 0.098, 95% CI: 0.928 approximately 2.404) the risks of CWP in those with FASL-844TT genotype and FASL-844TC genotype were respectively higher than those with FASL-844CC genotype (P = 0.039, 95% CI: 1.088 approximately 27.358, P = 0.089, 95% CI: 0.852 approximately 2.101). The frequencies of genotypes of FASL-844T > C were significantly different between CWP patients with exposure year > or = 25 and < 25. The risk of CWP with FASL-844TT genotype was significantly higher than that of FASL-844TT + TC (P = 0.054, 95% CI: 0.971 approximately 23.833). The risk of CWP patients with FASL-844TT/CT + FAS-1377GA genotype was 1.810-fold than the patients with FASL-844CC + FAS-1377GG genotype. The risk of CWP patients with FASL-844TT/CT + FAS-670AG genotype was 2.117-fold than the patients with FASL-844CC + FAS-670AA genotype. The risk of CWP patients with FASL-844TT/TC + FAS-1377GA/AA + FAS-670AG/GG genotype was 2.043-fold than the patients with FASL-844CC + FAS-1377GG+FAS-670AA genotype.

CONCLUSIONFAS-1377G > A, FAS-670A > G and FASL-844T > C gene polymorphisms may not be associated with the susceptibility of CWP in Han nationality, but these three gene polymorphisms and their joint actions may influence on the progression of CWP.

Adult ; Aged ; Aged, 80 and over ; Anthracosis ; genetics ; China ; Fas Ligand Protein ; genetics ; Female ; Genetic Predisposition to Disease ; Humans ; Male ; Middle Aged ; Polymorphism, Genetic ; fas Receptor ; genetics

The aim of this study was to investigate the effect of diallyl disulfide (DADS) on the apoptosis of K562 cells and to explore the mechanism of K562 apoptosis induced by DADS. The K562 cells were treated with different concentrations of DADS for 24, 48 and 72 hours. The concentrations of DADS were as follows: 0 (control group), 10, 20, 40 and 80 mg/L. The morphologic changes of leukemia K562 cells treated with DADS were observed by Hoechst33 258 staining. The apoptosis of K562 cells treated with different concentrations of DADS for 24, 48 and 72 hours was analyzed by flow cytometry. The mRNA expression changes of Fas and FasL were detected by reverse transcription-polymerase chain reaction (RT-PCR) after K562 cells were treated with different concentrations of DADS for 48 hours. The results indicated that the characteristics of apoptosis in K562 cells induced by DADS were as follows: reduction of nucleus, chromatin condensation and nuclear membrane rupture. The flow cytometry with PI straining showed that after 24 hours of DADS treatment the apoptosis rate of K562 cells increased from 11.60 ± 0.83% at the concentration of 10 mg/L to 37.94 ± 0.87% at the concentration of 40 mg/L. The apoptosis rate of K562 cells increased from 37.94 ± 0.87% (24 hours) to 47.02 ± 0.66% (72 hours) after treatment with DADS of 10 mg/L increasing to 40 mg/L DADS. The Fas mRNA expression levels of the related apoptotic genes increased after K562 cells were treated with different concentrations of DADS for 48 hours, while FasL mRNA expression decreased significantly after DADS treatment for 48 hours, compared with those in the control group (p < 0.05). It is concluded that DADS can induce the apoptosis of human leukemia K562 cells in a time-and concentration-dependent manners. The activation of Fas/FasL pathway may play an important role in the K562 cell apoptosis induced by DADS, which is associated with increasing Fas gene expression and decreasing FasL gene expression.
Allyl Compounds ; pharmacology ; Apoptosis ; drug effects ; Disulfides ; pharmacology ; Fas Ligand Protein ; metabolism ; Gene Expression Regulation, Leukemic ; Humans ; K562 Cells ; Signal Transduction ; fas Receptor ; metabolism

The purpose of this study was to investigate the expression of Fas, Fas ligand (FasL) and CD80 and function of FasL on the surface of acute myelomonocytic leukemia cells from WEHI-3 line. The expression of Fas, FasL and CD80 on the surface of WEHI-3 were detected by flow cytometry, the apoptosis of YAC-1 cell induced by FasL on the surface of WEHI-3 were detected by (3)H-TdR incorporation. The results showed that the expression rate of Fas, FasL and CD80 on the surface of WEHI-3 cells were (6.75 +/- 2.31)% (n = 5), (63.73 +/- 5.23)% (n = 5) and (5.06 +/- 0.41)% (n = 5) respectively. The apoptosis rate of YAC-1 cells (target cells) co-cultured with WEHI-3 cells (Effector cells) at the rate of 1:3, 1:10 and 1:30 were (26 +/- 4.5)%, (35 +/- 3.2)% and (43 +/- 2.7)% (n = 5) respectively. It is concluded that WEHI-3 cells have high expression of FasL and low expression of Fas and CD80 on their cell membrane, and can induce the apoptosis of Fas(+) YAC-1 cells.
Apoptosis ; physiology ; B7-1 Antigen ; biosynthesis ; Cell Membrane ; metabolism ; Fas Ligand Protein ; biosynthesis ; Humans ; Leukemia, Myelomonocytic, Acute ; metabolism ; pathology ; Tumor Cells, Cultured ; fas Receptor ; biosynthesis

The aim of this study was to investigate the effects of the traditional Chinese medicine psoralen (PSO) plus long wave ultraviolet A (PUVA) on apoptosis in HL-60 leukemia cells and its mechanism. The effect of PUVA on HL-60 cell growth was assayed by MTT method and the changes of ultrastructure of cells were observed by electron microscopy. The apoptosis ratios, changes of mitochondrial membrane potential, expression of Fas and FasL protein and Fas and FasL mRNA were detected by FCM and fluorescent quantitation RT-PCR respectively. The expression of Caspase 8 and Caspase 3 protein were detected by immunocytochemistry (ICC). The results showed that the growth of HL-60 cells were inhibited by PUVA in time-and concentration-dependent manner through inducing cell apoptosis. When the irradiation time of long wave ultraviolet A lasted 15 minutes and the concentration of PSO was 80 microg/ml, the inhibition of HL-60 cell proliferation and apoptosis ratios reached the peak. There were obvious apoptotic ultrastructure changes and decrease of mitochondrial membrane potential in HL-60 cells after treatment with PUVA. The expression of Fas mRAN increased and expression of FasL mRNA decreased after treating with PUVA for 4 hours, and the same results of Fas, FasL expression on protein level were obtained also after treating with PUVA for 24 hours. The expression of caspase 8 and caspase 3 protein enhanced and reached the peak after treating with PUVA for 8 hours. It is concluded that the PUVA can inhibit the growth of HL-60 cells and induce apoptosis of these cells. The possible mechanism is supposed to be up-regulating Fas, down-regulating FasL levels and then activating the levels of caspase 8 and caspase 3. The decreasing of mitochondrial membrane potential may be involved in this process probably.
Apoptosis ; drug effects ; radiation effects ; Caspase 3 ; metabolism ; Caspase 8 ; metabolism ; Fas Ligand Protein ; metabolism ; Ficusin ; pharmacology ; HL-60 Cells ; Humans ; Ultraviolet Rays ; fas Receptor ; metabolism

AIMTo investigate the effect of ligustrazine (LGT) on expression of Fas/FasL mRNA during pulmonary ischemia/reperfusion injury (PI/RI) in the rabbits.

METHODSSingle lung ischemia/reperfusion animal model was used in this study. The rabbits were randomly divided into three groups (n = 30, in each): sham operated group (Sham), I/R group (I/R) and I/R + LGT group (I/R + LGT). Changes of several parameters which included apoptotic index (AI), wet to dry ratio of lung tissue weight (W/D) and index of quantitative assessment of histologic lung injury (IQA) were measured at 1h, 3h, 5h after reperfusion in lung tissue. Meanwhile the location and expression of Fas/FasL mRNA were observed. Lung tissue was prepared for light microscopic and electron microscopic ob servation at 1 h, 3 h, 5 h after reperfusion.

RESULTSAs compared with group I/R, Fas/FasL mRNA slightly expressed in intima and extima of small pulmonary artery, alveoli, and bronchiole epithelia in group LGT. The values of AI, W/D and IQA showed significantly lower in group I/R + LGT than that in group I/R at 1 h, 3 h, 5 h after reperfusion in lung tissue (P < 0.01 and P < 0.05). Meanwhile, abnormal changes of the lung tissue in morphologically were lessen markedly in group I/R + LGT.

CONCLUSIONLigustrazine has notable protective effects on PI/RI in rabbits by inhibiting Fas/FasL mRNA express in lung tissue and decreasing apoptosis.

Animals ; Apoptosis ; Fas Ligand Protein ; metabolism ; Lung ; blood supply ; Lung Injury ; metabolism ; pathology ; Pyrazines ; pharmacology ; RNA, Messenger ; genetics ; Rabbits ; Reperfusion Injury ; metabolism ; pathology ; fas Receptor ; metabolism