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A derivative of the natural macrocyclic lactone sirolimus with immunosuppressant and anti-angiogenic properties. In cells, everolimus binds to the immunophilin FK Binding Protein-12 (FKBP-12) to generate an immunosuppressive complex that binds to and inhibits the activation of the mammalian Target of Rapamycin (mTOR), a key regulatory kinase. Inhibition of mTOR activation results in the inhibition of T lymphocyte activation and proliferation associated with antigen and cytokine (IL-2, IL-4, and IL-15) stimulation and the inhibition of antibody production. (NCI05)
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Growth/differentiation factor 15 (308 aa, ~34 kDa) is encoded by the human GDF15 gene. This protein plays a role in both tissue differentiation and signal transduction.
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An immunoglobulin isotype (subclass). This isotype has the unique ability to bind with high affinity to IgE receptors (FceRI) on mast cells and basophils and induce degranulation and cytokine production by these cells when they are crosslinked by antigen. In addition to a central role in atopy and allergic responses, it has been speculated that IgE-mediated mast cell degranulation, by its release of mediators that increase vascular permeability, has an important role in the initiation of immune response in general.
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Interleukin-10 (178 aa, ~21 kDa) is encoded by the human IL10 gene. This protein plays a role in the negative regulation of cytokine expression.
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Exhibiting a broad range of biological activities on T and natural killer cells, Interleukin-12 is a disulfide-bonded heterodimeric cytokine composed of a 35-kD IL12A subunit (IL-6 Superfamily) and a 40-kDa IL12B subunit (Type I Cytokine Receptor 3 Family). IL12 stimulates T-cell-independent production of IFN-gamma by PBMCs, enhances NK cell lytic activity, acts as a growth factor for T- and NK-cells, and is important for Th1 and Th2 cell differentiation. Lymphocyte responses to IL12 require NOS2A and are mediated by STAT4 activator of transcription. (NCI)
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A heterodimeric cytokine composed of interleukin-12 subunit beta and interleukin-23 subunit alpha. This complex binds to the interleukin-23 receptor complex, which activates the JAK-STAT signaling pathway and modulates the proliferation, differentiation and effector functions of T-lymphocytes, natural killer cells and some myeloid lineage cells.
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A natural macrocyclic lactone produced by the bacterium Streptomyces hygroscopicus, with immunosuppressant properties. In cells, sirolimus binds to the immunophilin FK Binding Protein-12 (FKBP-12) to generate an immunosuppressive complex that binds to and inhibits the activation of the mammalian Target Of Rapamycin (mTOR), a key regulatory kinase. This results in inhibition of T lymphocyte activation and proliferation that occurs in response to antigenic and cytokine (IL-2, IL-4, and IL-15) stimulation and inhibition of antibody production. (NCI04)
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A macrolide isolated from Streptomyces tsukubaensis. Tacrolimus binds to the FKBP-12 protein and forms a complex with calcium-dependent proteins, thereby inhibiting calcineurin phosphatase activity and resulting in decreased cytokine production. This agent exhibits potent immunosuppressive activity in vivo and prevents the activation of T-lymphocytes in response to antigenic or mitogenic stimulation. Tacrolimus possesses similar immunosuppressive properties to cyclosporine, but is more potent.
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Tumor necrosis factor (233 aa, ~26 kDa) is encoded by the human TNF gene. This protein is involved in the induction of cytokine expression, the stimulation of cell proliferation and the positive regulation of cell differentiation.