Mouse Anti-Canine TNF monoclonal antibody for ELISA(Cap), ICC/IF. Tumor necrosis factor alpha (TNF-alpha), also known as cachectin, is the prototypic ligand of the TNF superfamily. It is a pleiotropic molecule that plays a central role in inflammation, apoptosis, and immune system development. TNF-alpha is produced by a wide variety of immune and epithelial cell types. Canine TNF-alpha consisits of a 35 amino acid (aa) cytoplasmic domain, a 21 aa transmembrane segment, and a 177 aa extracellular domain (ECD). Within the ECD, canine TNF-alpha share 84-94% aa sequence identity with equine, feline, human, porcine, and rhesus and 69-77% with bovine, cotton rat, mouse, and rat with TNF-alpha. The 26 kDa type 2 transmembrane protein is assembled intracellularly to form a noncovalently linked homotrimer. Ligation of this complex induces reverse signaling that promotes lymphocyte co-stimulation but diminishes monocyte responsiveness. Cleavage of membrane bound TNF-alpha by TACE/ADAM17 releases a 55 kDa soluble trimeric form of TNF-alpha. TNF-alpha trimers bind the ubiquitous TNF RI and the hematopoietic cell-restricted TNF RII, both of which are also expressed as homotrimers. TNF-alpha regulates lymphoid tissue development through control of apoptosis. It also promotes inflammatory responses by inducing the activation of vascular endothelial cells and macrophages. TNF-alpha is a key cytokine in the development of several inflammatory disorders. It contributes to the development of type 2 diabetes through its effects on insulin resistance and fatty acid metabolism.
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