GMP TNF-alpha/TNFSF2 Protein, Human

TNF alpha is produced by various types of cells including macrophages, monocytes, neutrophils, T cells, and NK-cells^[2].
The amino acid sequence of human TNF alpha protein has low homology between mouse, rat, bovine, cynomolgus TNF alpha protein. While, human TNF alpha shares 94.85% aa sequence identity with cynomolgus TNF alpha protein, mouse TNF alpha shares 94.47% aa sequence identity with rat TNF alpha protein.
TNF alpha exists in two forms; a type II transmembrane protein (tmTNF-α) and a mature soluble protein (sTNF-α). TNF-α binds to its receptors, mainly TNFR1 and TNFR2, and then transmits molecular signals for biological functions such as inflammation and cell death. Both sTNF-α and tmTNF-α activate TNFR1, and process a death domain (DD) that interacts with the TNFR1-associated death domain (TRADD) adaptor protein. The TNFR2 signaling pathway is mainly activated by tmTNF-α. TNFR1 signaling tends to be pro-inflammatory and apoptotic. TNFR2 results in NF-κB and MAPKs and AKT activation, TNFR2 activation is associated with homeostatic bioactivities such as tissue regeneration, cell proliferation, and cell survival, as well as host defense and inflammation^[1].
TNF-alpha is critical for normal immune response, abnormal secretion TNF alpha activates synovial fibroblasts, keratinocytes, osteoclasts, induces rheumatoid arthritis, inflammatory bowel disease, psoriatic arthritis (PsA), and noninfectious uveitis (NIU)^[3]. TNF alpha positively regulates endogenous TNF-α expression levels independently of Pgp efflux activity, induces IHF cells proliferation^[4]. TNF alpha in tissues may promote cancer growth, invasion, and metastasis. Besides, TNF alpha stimulates NF-κB pathway via TNFR2 and anti-TNF-α MAb significantly suppresses the tumor development in colitis-associated cancer (CAC) mouse^[5]. TNF alpha as a proneurogenic factor activates the SAPK/JNK pathway and can facilitate neuronal replacement and brain repair in response to brain injury^[6].

TNF alpha (human) (0, 10, 15, 20, 30, 50 ng/mL; 24, 48 h) reduces KB-C1 cells viability at 30 ng/mL after 48 h, reduces pro-caspase-3, cleaved caspase-3 expression in KB-C1 and KB-3-1 cells^[4].
TNF alpha (human) (10, 15 ng/mL; 24 h) significantly increases the mRNA levels of Pgp (ABCB1) in KB-3-1 cells, and promotes expressive reduction on total Pgp protein levels and a slightly decreases in cell surface-Pgp in KB-C1 cells, and stimulates IHF cells proliferation, probably via ERK activation^[4].

TNF alpha (human) (100 µg; osmium pump in back; daily for 7 days) significantly increases in the number of inflammatory cells and the degree of synovial inflammation is significantly exacerbated in twenty-four SCID-HuRAg mice^[7].