"Shenandoah Biotechnology"

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Tumor necrosis factor receptor type 1 (TNFR-1) is expressed in most tissues and is activated by soluble and membrane-bound tumor necrosis factor alpha (TNF-α). TNFR-1 activates NF-κB and MAPK pathways to induce inflammation, promote apoptotic cell death, inhibit tumorigenesis, and inhibit viral replication.

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Cytokines for expansion and cell culture of human hematopoietic stem cells to progenitor cells. Hematopoietic stem cells are self renewing pluripotent cells often characterized by the expression of CD34. Studies have shown that decreased expression of CD34 tends to correlate with the decreased self renewal properties and pluripotent potential. Culturing CD34+ cells in a cytokine mixture of SCF, FLT-3 Ligand, IL-6 and IL-3 for short time periods allows rapid expansion of immature and more mature hematopoietic progenitor cells in cord blood or bone marrow preparations. If the goal is to only expand the most immature progenitor and stem cells, it is recommended that a combination of TPO, SCF and FLT-3 Ligand are used (Catalog: PB-500-03). Either cytokine combination can also be supplemented with other cytokines to promote specific lineages.

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Glial cell-derived neurotrophic factor (GDNF) is a neurotrophic factor that signals through a multicomponent receptor system to activate receptor tyrosine kinase RET signaling. GDNF promotes dopamine uptake, prevents motor neuron apoptosis, and supports the survival and differentiation of neurons.

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Interleukin 21 (IL-21) is a member of the common-gamma chain family of cytokines that are involved in immunoregulation. IL-21 is normally expressed by activated CD4+ T cells and is aberrantly expressed in Hodgkin lymphoma cells. The IL-21 receptor (IL-21R) activates the JAK/STAT signaling pathway and is expressed on T, B, and natural killer (NK) cells.

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Interleukin-1 receptor antagonist (IL-1RA) binds the interleukin 1 receptor (IL-1R) to antagonize interleukin 1 alpha and beta signaling. IL-1RA is secreted by immune cells, epithelial cells, hepatocytes, and adipocytes to inhibit IL-1-induced inflammation. IL-1RA therapy is used to treat auto-inflammatory diseases such as diabetes and rheumatoid arthritis.

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Interleukin 17E (IL-17E), also known as IL-25, is a member of the IL-17 family of cytokines. IL-17E binds to the IL-17RB receptor to stimulate the secretion of the proinflammatory interleukin 8 (IL-8) chemokine and to induce the activation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB).

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Interleukin-19 (IL-19) is a member of the interleukin 10 (IL-10) cytokine family and is produced by B cells and monocytes. IL-19 binds the interleukin 20 receptor complex (IL-20R) to activate STAT3 signaling. IL-19 induces interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-a) expression in monocytes, and promotes T helper 2 (Th2) cell-mediated immune responses. IL-19 production is up-regulated in resting monocytes following granulocyte-macrophage colony-stimulating factor (GM-CSF) or lipopolysaccharide (LPS) stimulation.

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Heparin-binding EGF-like growth factor (HB-EGF) is a member of the epidermal growth factor (EGF) family and is expressed by monocytes and macrophages. HB-EGF is the predominant growth factor involved in epithelialization during wound healing. HB-EGF signals through the receptor tyrosine kinase ErbB2 to maintain adult heart homeostasis, and promotes cardiac valve development through binding in high affinity to the epidermal growth factor receptor (EGFR). HB-EGF binds the the ErbB4 receptor tyrosine kinase to mediate implantation of the human blastocyst. HB-EGF also functions as a potent mitogen for fibroblasts and smooth muscle cells.

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Epidermal growth factor (EGF) is a growth factor that stimulates the proliferation, differentiation, and survival of epithelial and epidermal cells. EGF contains three intramolecular disulfide bonds and binds in high affinity to the epidermal growth factor receptor (EGFR). EGF is overexpressed in multiple tumor cell lines and promotes resistance to chemotherapy and radiation treatments.

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Cytokines for cell culture of human DIPG and other glioma cells. A glioma is a generic term used to describe tumors that arise from the glia tissue of the brain that supports and surrounds neurons. Diffuse Intrinsic Pontine Glioma (DIPG) is a pediatric brain tumor that originates in the brainstem. Cells isolated from these childhood tumors are successfully cultured ex vivo with EGF, FGF-basic (or FGF-2), and PDGFs (AA and BB).

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Transforming growth factors (TGFs) are multifunctional peptides that regulate growth and differentiation in most cell types. The TGF-β family of proteins signal through serine/threonine kinase receptors. TGF-β isoforms (TGF-β1, -β2, and –β3) have overlapping, yet distinct biological actions in developing and adult tissues. TGF-β3 is an important factor in regulating cell adhesion and accelerating wound repair. TGF-β3 also functions during osteoblast proliferation, chemotaxis, and collagen synthesis.

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Placenta growth factor (PlGF) is a member of the vascular endothelial growth factor (VEGF) family and promotes endothelial cell growth and angiogenesis. PlGF is secreted as a homodimer and may also form a heterodimer with VEGF. PlGF is detected in the placenta, heart, lungs, thyroid, and adipose tissues. Circulating PlGF levels are correlated with colorectal and renal cancers, as well as atherosclerosis and ischemic heart disease. There are four alternatively spliced PlGF isoforms (PlGF-1, PlGF-2, PlGF-3, and PlGF-4), each with unique secretion patterns and heparin-binding affinities. PlGF-3 lacks a heparin-binding domain and signals through the VEGFR-1 receptor.

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Macrophage inflammatory protein-4 (MIP-4), also called CCL18, is a chemokine expressed in the lymph nodes, lungs, placenta, and bone marrow. MIP-4 receptors include the chemokine receptor 8 (CCR8), the G protein-coupled receptor 30 (GPR30), and the phosphatidylinositol transfer protein membrane-associate 3 (PITPNM3). MIP-4 acts as a chemoattractant for naive T cells, CD4+ T cells, CD8+ T cells, and nonactivated lymphocytes. Further, MIP-4 promotes breast cancer metastasis and attenuates the activation of acute lymphocytic leukemia B cells.

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Interferon gamma-induced protein 10 (IP-10), or CXCL10, is a chemokine secreted by monocytes, endothelial cells, and fibroblasts in response to interferon gamma (IFN-γ). IP-10 functions as a chemoattractant for activated T cells, monocytes, dendritic, and natural killer (NK) cells that express the G protein-coupled receptor CXCR3. IP-10 is an important factor in autoimmune diseases such as Hashimoto's thyroiditis, Graves' disease, and Type 1 diabetes mellitus.

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Placenta growth factor (PlGF) is a member of the vascular endothelial growth factor (VEGF) family and promotes endothelial cell growth and angiogenesis. PlGF is secreted as a homodimer and may also form a heterodimer with VEGF. PlGF is detected in the placenta, heart, lungs, thyroid, and adipose tissues. Circulating PlGF levels are correlated with colorectal and renal cancers, as well as atherosclerosis and ischemic heart disease. There are four alternatively spliced PlGF isoforms (PlGF-1, PlGF-2, PlGF-3, and PlGF-4), each with unique secretion patterns and heparin-binding affinities. PlGF-3 lacks a heparin-binding domain and signals through the VEGFR-1 receptor.

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Eotaxin, also known as Eotaxin-1 and CCL11, is a chemokine that recruits eosinophils to sites of allergic inflammation. Eotaxin signals through the G protein-coupled chemokine receptors CCR2, CCR3, and CCR5.