Tumor Necrosis Factor (TNF) is a cytokine that can directly kill tumor cells without obvious toxicity to normal cells. TNF is not heat-resistant and will be inactivated at 70℃ for 30 minutes. It is one of the most effective bioactive factors to kill tumor directly. Tumor necrosis factor can be divided into TNF-αand TNF-β, and about 30 kinds of TNF family are found in addition to these two types. umor necrosis factor (TNF) is a small molecular protein secreted by macrophages and its content in normal human serum is 4.3±2.8mg/L. TNF-α is secreted mainly by mononuclear macrophages. TNF-β is secreted primarily by activated T lymphocytes.
Properties of TNF protein
The structure and function of the Tumor necrosis factor receptor (TNFR)
TNFR can be divided into two types: TNFR1 is expressed in all types of cells and plays a major role in cytolytic activity. TNFR2 is only expressed in immune and endothelial cells and is associated with signaling and T cell proliferation. Both TNFRS are glycoproteins, including extracellular, transmembrane, and intracellular regions. The extracellular region has 28% homology, but there is no homology in the cytoplasmic region, which may be related to the mediation of different signal transduction pathways. Several studies have confirmed that tumor necrosis factor exerts its biological activity mainly through interaction with TNF-R1. TNF protein binds to the extracellular region of TNF-R1 to induce tnf-r1 aggregation and release of death domain silencing (SODD), and TRADD then binds to the death domain of TNF-R1 to recruit more junction proteins, such as RIP, TRAF-2 and FADD. These adaptor proteins recruit other important proteins involved in signal transduction to function. At present, little is known about the structure and function of TNF-R2, but it lacks a death domain and therefore cannot promote the process of apoptosis. However, TNF-R2 can interfere with programmed cell death (PCD) by activating the NF-κB and JNK pathways or inhibiting TRAF-2.
The distribution of TNFR
TNFR exists on the surface of a variety of normal and tumor cells. Generally, the number of receptors per cell is 500 ~ 5000 / cell. For example, ME-800 tumor cell line TNFR is about 2000 / cell, and Kd is 2 × 10-10M. The number and affinity of TNFR on different cell surfaces do not seem to be parallel to the cell's sensitivity to TNF-α.
Soluble tumor necrosis factor receptor
TNF-binding protein (TNF-BP) is a soluble form of TNFR. There are sTNFRⅠ (TNF-BPⅠ) and sTNFRⅡ (TNF-BPⅡ). It is generally believed that sTNFR has the function of limiting TNF activity or stabilizing TNF, and it also has an important regulatory role in the cytokine network. TNF-BP specifically binds TNF to inhibit TNF activity, such as inhibiting its cytotoxic activity and inducing IL-1 production, and can promote the growth of Meth A virus subcutaneously inoculated, which may be one of the mechanisms of tumor escape host anti-tumor. TNF-BP in normal human serum is 1-2 ng / ml, which can also be found in normal pregnancy urine. Its content increases during inflammation, endotoxemia, meningococcal infections, SLE, HIV infection, renal insufficiency, and tumors. Soluble TNFR can effectively reduce the pathological changes of adjuvant arthritis and septic shock.