IL-17A/TNF alpha Antibodies

Target Information

Interleukin-17A (IL-17A, CTLA-8) is a CD4+ T cell-derived cytokine that promotes inflammatory responses in cell lines and is elevated in rheumatoid arthritis, asthma, multiple sclerosis, psoriasis, and transplant rejection. IL-17A is a 32 kDa long, disulfide-linked homodimer consisting of 136 amino acids that is a member of a six-species family of proteins (IL-17A-17F) and signals through the IL-17 receptor (IL-17R/CDw217). High levels of IL-17A homodimer are produced by activated peripheral blood CD4+ T-cells, and IL-17A also enhances expression of the intracellular adhesion molecule-1 (ICAM-1) in human fibroblasts. In particular, human IL-17A also stimulates epithelial, endothelial, or fibroblastic cells to secrete IL-6, IL-8, G-CSF, and PGE2. In the presence of human IL-17A, fibroblasts can sustain the proliferation of CD34+ hematopoietic progenitors and induce maturation into neutrophils. Mouse, rat, and human IL-17A can induce IL-6 secretion in mouse stromal cells, indicating that all homologs can recognize the mouse receptor. IL-17A regulates the activities of NF-kappa B and mitogen-activated protein kinases, stimulates the expression of IL-6 and cyclooxygenase-2 (PTGS2/COX-2), and enhances the production of nitric oxide (NO).

TNF alpha is a multifunctional proinflammatory cytokine that belongs to the tumor necrosis factor (TNF) superfamily. This cytokine is mainly secreted by macrophage and bind to its receptors, TNFRSF1A/TNFR1 and TNFRSF1B/TNFBR. TNF alpha is involved in the regulation of immune cells, cell proliferation, differentiation, apoptosis, lipid metabolism, and coagulation. TNF alpha exists as a multimer of two, three, or five noncovalently linked units, but shows a single 17 kDa band following SDS-PAGE under non-reducing conditions. Knockout studies in mice also suggested the neuroprotective function of TNF alpha, and has been observed to causes tumor necrosis when injected into tumor-bearing mice. Other functions of TNF-alpha include its role in the immune response to bacterial, viral, parasitic and certain fungal infections, as well as its role in the necrosis of specific tumors. TNF alpha causes cytolysis or cytostasis of certain transformed cells, being synergistic with interferon-gamma in its cytotoxicity. This cytokine has been implicated in a variety of diseases, including autoimmune diseases, insulin resistance, and cancer.