BACKGROUND Melatonin, which is well-known antioxidant, has been shown to have anti-invasive properties for glioma. However, little is known about the effects of melatonin on the migration and invasion of glioma cells under hypoxia, which is essential for the progress of the microenvironment of the tumor. In addition, the focus of adhesion kinase (FAK) and a proline-rich tyrosine kinase 2 (Pyk2) are closely associated with cell migration and invasion. Therefore, we investigated the possible role of this kinase and related signal in the regulation of the behavior of a human U251 glioma cells with melatonin under hypoxia.
METHOD The ability of U251 cells migration and invasion of glioma determined by the wound healing and transwell in vitro assays. Production of intracellular reactive oxygen species (ROS) were measured using a fluorescent probe 6-carboxy-2 ‘, 7’-dichorodihydrofluorescein diacetate (DCFH-DA). experiment immunofluorescence and Western blotting analysis is used to detect the protein expression levels. Disturb small RNA (siRNA) was used to silence the expression of specific genes.
RESULTS Pharmacological concentration (1 mM) of melatonin significantly inhibited the migration and invasion of human glioma U251 cells under hypoxia. The inhibitory effect of melatonin is accompanied by decreased phosphorylation of FAK and Pyk2, and decreased expression of alpha v beta 3 (αvβ3) integrin. Additionally, αvβ3 integrin inhibition by siRNA reduces phosphorylation of FAK / Pyk2 and shows anti-tumor effects are the same as melatonin, indicating the involvement of αvβ3 integrin- FAK / Pyk2 pathway in anti-migration and anti-invasive melatonin. It was also found that melatonin treatment decreased ROS levels in U251 glioma cells cultured under hypoxia. ROS inhibitor apocynin not only inhibit integrin αvβ3 expression and phosphorylation of FAK and Pyk2 level, but also suppresses the migration and invasive capacity U251 glioma cells under hypoxia.
CONCLUSION These results suggest that melatonin exerts anti-migratory effect and anti-invasive glioma cells in response to hypoxia via ROS-αvβ3 integrin-FAK / Pyk2 signal path. This provides evidence that melatonin may be a potential therapeutic molecules targeting the hypoxic micro glioma.
Involvement of ROS-alpha v beta 3 integrin-FAK/Pyk2 in the inhibitory effect of melatonin on U251 glioma cell migration and invasion under hypoxia.
Epithelial V-like antigen mediate the efficacy of anti-integrin alpha₄ treatment in a mouse model of multiple sclerosis.
Natalizumab inhibit the transmigration of activated T lymphocytes into the brain and is efficacious in multiple sclerosis (MS). However, from the perspective of pharmacogenomics, efficacy and safety in certain patients remains unclear. Here our aim is to analyze the effects of epithelial V-like antigen (EVA) on the anti-alpha₄ integrin (VLA4) efficacy in a mouse model of MS, experimental autoimmune encephalomyelitis (EAE). EVA has previously been characterized in human CD4 + T lymphocytes, mouse thymus development, and epithelial cells of the choroid plexus.
Further analysis here showed expression in B lymphocytes, and increase lymphocyte EVA⁺ after immunization. The following active induction of EAE model MOG³⁵⁻⁵⁵ active immunization, EVA deficient mice developed EAE injury and white matter tissue is more severe than the wild type control. This severe EAE phenotype did not respond to anti-VLA4 treatment. In both the control condition and the anti-VLA4 antibodies, these mice show persistent CNS invasion mature B lymphocytes (CD19⁺, CD21⁺, sIgG⁺), increased serum levels of autoantibodies, and appendages broad and IgG deposition in the lesion containing CD5⁺IgG⁺ cells.
Description: Interleukin-17A Human Recombinant produced in E.Coli is a homodimeric, non-glycosylated polypeptide chain containing a total of 264 amino acids (2 chains of 132 aa) and having a molecular mass of 31kDa. ;The IL-17 is purified by proprietary chromatographic techniques.
Description: IL-17 Antibody: Interleukin 17 (IL-17) is a family of pro-inflammatory cytokines produced by activated T cells and is thought to have a major role in the initiation and perpetuation of rheumatoid arthritis. IL-17 regulates the activities of NF-κB and mitogen-activated protein kinases such as ERK and JNK. In addition, IL-17 stimulates the expression of IL-6 and cyclooxygenase-2 and enhances the production of nitric oxide. IL-17-producing T helper cells (TH-17 cells) have been the subject of much attention due to the importance of IL-17 in the pathogenesis of autoimmune inflammation. Because of its role in autoimmune diseases, it is thought that targeting the production and action of IL-17 would be beneficial therapeutically in these diseases.
Description: IL-17 Antibody: Interleukin 17 (IL-17) is a family of pro-inflammatory cytokines produced by activated T cells and is thought to have a major role in the initiation and perpetuation of rheumatoid arthritis. IL-17 regulates the activities of NF-κB and mitogen-activated protein kinases such as ERK and JNK. In addition, IL-17 stimulates the expression of IL-6 and cyclooxygenase-2 and enhances the production of nitric oxide. IL-17-producing T helper cells (TH-17 cells) have been the subject of much attention due to the importance of IL-17 in the pathogenesis of autoimmune inflammation. Because of its role in autoimmune diseases, it is thought that targeting the production and action of IL-17 would be beneficial therapeutically in these diseases.
Description: IL-17 Antibody: Interleukin 17 (IL-17) is a family of pro-inflammatory cytokines produced by activated T cells and is thought to have a major role in the initiation and perpetuation of rheumatoid arthritis. IL-17 regulates the activities of NF-κB and mitogen-activated protein kinases such as ERK and JNK. In addition, IL-17 stimulates the expression of IL-6 and cyclooxygenase-2 and enhances the production of nitric oxide. IL-17-producing T helper cells (TH-17 cells) have been the subject of much attention due to the importance of IL-17 in the pathogenesis of autoimmune inflammation. Because of its role in autoimmune diseases, it is thought that targeting the production and action of IL-17 would be beneficial therapeutically in these diseases.
Description: IL-17 Antibody: Interleukin 17 (IL-17) is a family of pro-inflammatory cytokines produced by activated T cells and is thought to have a major role in the initiation and perpetuation of rheumatoid arthritis. IL-17 regulates the activities of NF-κB and mitogen-activated protein kinases such as ERK and JNK. In addition, IL-17 stimulates the expression of IL-6 and cyclooxygenase-2 and enhances the production of nitric oxide. IL-17-producing T helper cells (TH-17 cells) have been the subject of much attention due to the importance of IL-17 in the pathogenesis of autoimmune inflammation. Because of its role in autoimmune diseases, it is thought that targeting the production and action of IL-17 would be beneficial therapeutically in these diseases.
Description: The originally described IL-17 protein, now known as IL-17A, is a homodimer of two 136 amino acid chains, secreted by activated T-cells that act on stromal cells to induce production of proinflammatory and hematopoietic bioactive molecules. Today, IL-17 represents a family of structurally-related cytokines that share a highly conserved C-terminal region but differ from one another in their N-terminal regions and in their distinct biological roles. The six known members of this family, IL-17A through IL-17F, are secreted as homodimers. IL-17A exhibits cross-species bioactivity between human and murine cells. Recombinant human IL-17A is a 31.3 kDa disulfide-linked homodimer of two 137 amino acid polypeptide chains.
Description: IL-17 Human Recombinant produced in HEK cells is a glycosylated homodimer, having a molecular weight range of 30-35kDa due to glycosylation.;The IL-17 is purified by proprietary chromatographic techniques.
Description: A competitive inhibition quantitative ELISA assay kit for detection of 17-Hydroxyprogesterone (17-OHP) in samples from serum, plasma, tissue homogenates, cell lysates, cell culture supernates or other biological fluids.
Description: A competitive inhibition quantitative ELISA assay kit for detection of 17-Hydroxyprogesterone (17-OHP) in samples from serum, plasma, tissue homogenates, cell lysates, cell culture supernates or other biological fluids.
Description: Interleukin-17 is a potent pro-inflammatory cytokine produced by activated memory T cells. There are at least six members of the IL-17 family in humans and in mice. As IL-17 shares properties with IL-1 and TNF-alpha, it may induce joint inflammation and bone and cartilage destruction. This cytokine is found in synovial fluids of patients with rheumatoid arthritis, and produced by rheumatoid arthritis synovium. It increases IL-6 production, induces collagen degradation and decreases collagen synthesis by synovium and cartilage and proteoglycan synthesis in cartilage. IL-17 is also able to increase bone destruction and reduce its formation. Blocking of interleukin-17 with specific inhibitors provides a protective inhibition of cartilage and bone degradation.
Description: Interleukin-17 is a potent pro-inflammatory cytokine produced by activated memory T cells. There are at least six members of the IL-17 family in humans and in mice. As IL-17 shares properties with IL-1 and TNF-alpha, it may induce joint inflammation and bone and cartilage destruction. This cytokine is found in synovial fluids of patients with rheumatoid arthritis, and produced by rheumatoid arthritis synovium. It increases IL-6 production, induces collagen degradation and decreases collagen synthesis by synovium and cartilage and proteoglycan synthesis in cartilage. IL-17 is also able to increase bone destruction and reduce its formation. Blocking of interleukin-17 with specific inhibitors provides a protective inhibition of cartilage and bone degradation.
Description: A polyclonal antibody raised in Rabbit that recognizes and binds to Human IL-17 . This antibody is tested and proven to work in the following applications:
Description: A polyclonal antibody raised in Rabbit that recognizes and binds to Human IL-17 . This antibody is tested and proven to work in the following applications:
Description: Quantitativecompetitive ELISA kit for measuring Chicken Interleukin 17, IL-17 in samples from serum, plasma, tissue homogenates. A new trial version of the kit, which allows you to test the kit in your application at a reasonable price.
Description: Quantitativecompetitive ELISA kit for measuring Chicken Interleukin 17, IL-17 in samples from serum, plasma, tissue homogenates. Now available in a cost efficient pack of 5 plates of 96 wells each, conveniently packed along with the other reagents in 5 separate kits.
Description: Quantitativesandwich ELISA kit for measuring Mouse Interleukin 17, IL-17 in samples from serum, plasma, tissue homogenates, cell culture supernates. A new trial version of the kit, which allows you to test the kit in your application at a reasonable price.
Description: Quantitativesandwich ELISA kit for measuring Mouse Interleukin 17, IL-17 in samples from serum, plasma, tissue homogenates, cell culture supernates. Now available in a cost efficient pack of 5 plates of 96 wells each, conveniently packed along with the other reagents in 5 separate kits.
Description: Quantitativesandwich ELISA kit for measuring Bovine Interleukin 17 (IL-17) in samples from serum, plasma, tissue homogenates. A new trial version of the kit, which allows you to test the kit in your application at a reasonable price.
Description: Quantitativesandwich ELISA kit for measuring Bovine Interleukin 17(IL-17) in samples from serum, plasma, tissue homogenates. Now available in a cost efficient pack of 5 plates of 96 wells each, conveniently packed along with the other reagents in 5 separate kits.
Description: Quantitativesandwich ELISA kit for measuring Canine Interleukin 17 (IL-17) in samples from serum, plasma, tissue homogenates. A new trial version of the kit, which allows you to test the kit in your application at a reasonable price.
Description: Quantitativesandwich ELISA kit for measuring Canine Interleukin 17(IL-17) in samples from serum, plasma, tissue homogenates. Now available in a cost efficient pack of 5 plates of 96 wells each, conveniently packed along with the other reagents in 5 separate kits.
Description: Quantitativesandwich ELISA kit for measuring Rat Interleukin 17, IL-17 in samples from serum, plasma, tissue homogenates. A new trial version of the kit, which allows you to test the kit in your application at a reasonable price.
Description: Quantitativesandwich ELISA kit for measuring Rat Interleukin 17, IL-17 in samples from serum, plasma, tissue homogenates. Now available in a cost efficient pack of 5 plates of 96 wells each, conveniently packed along with the other reagents in 5 separate kits.
Description: Quantitativesandwich ELISA kit for measuring Pig interleukin 17, IL-17 in samples from serum, plasma, tissue homogenates. A new trial version of the kit, which allows you to test the kit in your application at a reasonable price.
Description: Quantitativesandwich ELISA kit for measuring Pig interleukin 17, IL-17 in samples from serum, plasma, tissue homogenates. Now available in a cost efficient pack of 5 plates of 96 wells each, conveniently packed along with the other reagents in 5 separate kits.
Description: Quantitativesandwich ELISA kit for measuring Rabbit Interleukin 17, IL-17 in samples from serum, plasma, tissue homogenates. A new trial version of the kit, which allows you to test the kit in your application at a reasonable price.
Description: Quantitativesandwich ELISA kit for measuring Rabbit Interleukin 17, IL-17 in samples from serum, plasma, tissue homogenates. Now available in a cost efficient pack of 5 plates of 96 wells each, conveniently packed along with the other reagents in 5 separate kits.
Description: Interleukin-17A Rat Recombinant produced in E.Coli is a homodimeric, non-glycosylated polypeptide chain having a molecular mass of 30 kDa. ;The IL-17A Rat is purified by proprietary chromatographic techniques.
Description: Interleukin-17 Murine Recombinant produced in E.Coli is a homodimeric, non-glycosylated polypeptide chain containing a total of 268 (2x134 a.a.) amino acids and having a molecular mass of 30 kDa. ; The IL-17 is purified by proprietary chromatographic techniques.
Description: Interleukin-17A Human Recombinant produced in E.Coli is a single, non-glycosylated, Polypeptide chain containing 132 amino acids fragment (24-155) having a molecular weight of 19.62kDa and fused with a 4.5kDa amino-terminal hexahistidine tag. ;The IL-17A His is purified by proprietary chromatographic techniques.
Description: Quantitative sandwich ELISA for measuring Human IL-17 in samples from cell culture supernatants, serum, whole blood, plasma and other biological fluids.
Description: Quantitative sandwich ELISA for measuring Human IL-17 in samples from cell culture supernatants, serum, whole blood, plasma and other biological fluids.
Description: Quantitative sandwich ELISA for measuring Human IL-17 in samples from cell culture supernatants, serum, whole blood, plasma and other biological fluids.
Description: The originally described IL-17 protein, now known as IL-17A, is a disulfide linked homodimer, secreted by activated T-cells that act on stromal cells to induce production of proinflammatory and hematopoietic bioactive molecules. Today, IL-17 represents a family of structurally-related cytokines that share a highly conserved C-terminal region but differ from one another in their N-terminal regions and in their distinct biological roles. The six known members of this family, IL-17A through IL-17F, are secreted as homodimers. IL-17A exhibits cross-species bioactivity between human and murine cells. Recombinant murine IL-17A is a 30.0 kDa disulfide-linked homodimer of two 133 amino acid polypeptide chains.
Description: Quantitativesandwich ELISA kit for measuring Human Interleukin 17A (IL-17A/IL-17) in samples from serum, urine, cell culture supernates, tissue homogenates. A new trial version of the kit, which allows you to test the kit in your application at a reasonable price.
Description: Quantitativesandwich ELISA kit for measuring Human Interleukin 17A (IL-17A/IL-17) in samples from serum, urine, cell culture supernates, tissue homogenates. Now available in a cost efficient pack of 5 plates of 96 wells each, conveniently packed along with the other reagents in 5 separate kits.
Description: Quantitativesandwich ELISA kit for measuring Guinea pig Interleukin 17, IL-17 in samples from serum, plasma, tissue homogenates. A new trial version of the kit, which allows you to test the kit in your application at a reasonable price.
Description: Quantitativesandwich ELISA kit for measuring Guinea pig Interleukin 17, IL-17 in samples from serum, plasma, tissue homogenates. Now available in a cost efficient pack of 5 plates of 96 wells each, conveniently packed along with the other reagents in 5 separate kits.
Description: Quantitative sandwich ELISA for measuring Rat Interleukin 17 (IL-17) in samples from cell culture supernatants, serum, whole blood, plasma and other biological fluids.
Description: Quantitative sandwich ELISA for measuring Rat Interleukin 17 (IL-17) in samples from cell culture supernatants, serum, whole blood, plasma and other biological fluids.
Description: Quantitative sandwich ELISA for measuring Rat Interleukin 17 (IL-17) in samples from cell culture supernatants, serum, whole blood, plasma and other biological fluids.
Wild-type mice treated with a control antibody also showed that cells CD19⁺, CD21⁺, sIgG⁺ in the CNS during the peak of EAE severity of the disease and detected serum autoantibodies. In contrast, wild-type mice treated with anti-VLA4 exhibited reduce the level of serum autoantibodies compared to control wild type and KO mice EVA
