Death receptors induce apoptosis by intracellular signaling transmission and relate to body growth, development, disease and death. This paper reviews the structural character of death receptors, and the mechanisms by which apoptosis is induced. The biology and pathobiology of these death receptors in liver are discussed as well.
Apoptosis ; physiology ; GPI-Linked Proteins ; Humans ; Liver ; pathology ; physiology ; Receptors, TNF-Related Apoptosis-Inducing Ligand ; Receptors, Tumor Necrosis Factor ; physiology ; Receptors, Tumor Necrosis Factor, Member 10c ; Tumor Necrosis Factor Decoy Receptors ; fas Receptor ; physiology

OBJECTIVETo explore the enhanced sensitivity of leukemia cell line KG-1a to activated immune cell-mediated cytolysis after treated with resveratrol.

METHODSThe value of 50% inhibition concentration (IC₅₀) for KG-1a by resveratrol was analyzed using trypan blue staining. Peripheral blood mononuclear cells were separated, and then activated by interleukin (IL)-2 and IL-15. The sensitivity of KG-1a treated with and without resveratrol to activated immune cell-mediated cytolysis was assayed by lactate dehydrogenase (LDH) -releasing assay. The expression of tumor necrosis factor related apoptosis inducing ligand (TRAIL) on the surface of activated immune cells and its receptors (DR4/5 and DcR1/2) on the surface of KG-1a were detected by flow cytometry.

RESULTSResveratrol could inhibit the proliferation of KG-1a and IC50 at 24 h was 25 mmol/L. At a ratio of 10:1 or 20:1 between effect and target, the cytolytic rates of treated KG-1a by activated immune cells were (55.80 ± 10.88)% and (72.31 ± 13.06)%, significantly higher than (24.96 ± 9.25)% and (37.93 ± 5.21)% of untreated KG-1a (P<0.05). The expression of DR5 on the surface of KG-1a treated with resveratrol was (9.05 ± 3.57)%, significantly higher than (3.11 ± 0.54)% of untreated KG-1a (P<0.05). Conversely, the expression of DcR1 on the surface of treated KG-1a was (13.23 ± 3.56)%, lower than (53.75 ± 10.51)% of KG-1a (P<0.05). When TRAIL pathway on the surface of activated immune cells was blocked, the cytolytic rates of treated KG-1a were (35.97 ± 6.36)% and (49.80 ± 10.68)%, significantly lower than (52.92 ± 6.98)% and (70.73 ± 9.79)% of untreated KG-1a (P<0.05) at the same ratio of effector and target.

CONCLUSIONResveratrol could enhance cytolytic sensitivity of KG-1a by activated immune cells through TRAIL pathway.

Cell Line, Tumor ; Cell Proliferation ; drug effects ; Humans ; Leukemia ; metabolism ; pathology ; Leukocytes, Mononuclear ; drug effects ; immunology ; metabolism ; Male ; Receptors, TNF-Related Apoptosis-Inducing Ligand ; metabolism ; Receptors, Tumor Necrosis Factor, Member 10c ; metabolism ; Stilbenes ; pharmacology ; TNF-Related Apoptosis-Inducing Ligand ; metabolism

There exist two major apoptotic signaling pathways: the intrinsic mitochondria-mediated pathway, and the extrinsic death receptor-induced pathway. TNF-related apoptosis-inducing ligand (TRAIL), which is the ligand for death receptor 4 (DR4) and death receptor 5 (DR5) and induces apoptosis by ligation with DR4 or DR5. We review the characteristic of TRAIL and its receptors, the mechanism of apoptosis induced by TRAIL, the distribution of death receptors in cancer, and applications and prospects of TRAIL signaling pathway in the treatment of cancer.
Animals ; Antineoplastic Agents ; pharmacology ; therapeutic use ; Apoptosis ; drug effects ; Drug Delivery Systems ; GPI-Linked Proteins ; genetics ; metabolism ; Genetic Therapy ; Humans ; Neoplasms ; metabolism ; pathology ; therapy ; Receptors, TNF-Related Apoptosis-Inducing Ligand ; classification ; genetics ; metabolism ; Receptors, Tumor Necrosis Factor, Member 10c ; Signal Transduction ; TNF-Related Apoptosis-Inducing Ligand ; genetics ; metabolism ; pharmacology ; Tumor Necrosis Factor Decoy Receptors ; genetics ; metabolism

OBJECTIVETo evaluate the differentially expressed genes between the Stress fracture (SF) cases and controls.

METHODSTotal RNA was extracted and purified from peripheral blood sample of 3 SF cases and 3 controls who conducted a 1:1 matched case-control study, then used for Human Genome Array analysis. The hybridization data were analyzed using SAM software. Parts of these genes were analyzed and identified by real-time PCR.

RESULTSUpregulated and downregulated genes were 22 and 1, respectively. Thus the highest ratio and most significant cytokine was tumor necrosis factor receptor superfamily, member 10c (TNFRSF10C). The result of real-time PCR shows that TNFRSF10C was over-expressed in 3 cases and low-expressed in 1 case.

CONCLUSIONObvious difference exists in gene expression between SF cases and controls, showing there may be a lot of genes involving in the occurrence and development of SF. Meanwhile, the identification of the specific genes is helpful for biomechanics study, early diagnosis and screening of SF.

Case-Control Studies ; DNA, Complementary ; genetics ; Fractures, Stress ; blood ; metabolism ; GPI-Linked Proteins ; genetics ; metabolism ; Gene Expression ; Gene Expression Profiling ; Humans ; Male ; Military Personnel ; Oligonucleotide Array Sequence Analysis ; Receptors, Tumor Necrosis Factor, Member 10c ; Tumor Necrosis Factor Decoy Receptors ; genetics ; metabolism ; Young Adult