TNF-α: a Deep Dive into Its Molecular Mechanisms and Clinical Applications_ELK Biotechnology - (주)코아사이언스

TNF-α: a Deep Dive into Its Molecular Mechanisms

                      and Clinical Applications

 

Tumor Necrosis Factor-α (TNF-α) is a proinflammatory cytokine secreted by macrophages and monocytes, with a molecular mass of 17.4 kDa or 26 kDa, corresponding to the C-terminal extracellular domain of the full-length transmembrane protein. It can be secreted by a variety of cells, including adipocytes, activated monocytes, macrophages, B cells, T cells and fibroblasts. Among them, TNF mainly produced by macrophages is designated as TNF-α, which is involved in cell proliferation, metabolic activation, inflammatory responses and immune regulation processes.

Molecular Structure and Expression Regulation of TNF-α

Molecular Structure and Expression Regulation of TNF-αTNF-α is a homotrimeric protein derived from a 233-amino acid precursor. Cleavage by TACE releases a soluble 157-amino acid cytokine. Its expression is regulated by NF-κB and MAPK pathways, involving transcriptional control by factors like NF-κB and AP-1, and post-transcriptional modulation via mRNA stability elements such as AREs. Structurally, the monomer adopts a β-sheet "jelly-roll" fold, with trimer assembly driven by hydrophobic interactions. This configuration dictates receptor binding specificity and influences bioactivity, including in vivo stability and function.

TNF-α exerts its biological functions through two transmembrane receptors: TNFR1 (p55) and TNFR2 (p75). TNFR1 is widely expressed in various cell types, while TNFR2 is mainly expressed in immune cells and endothelial cells; activation of the two receptors triggers distinctly different downstream signals.

TNF-α acts via TNFR1 (p55, ubiquitous) and TNFR2 (p75, immune/endothelial cells). TNFR1 trimerizes upon binding, recruits TRADD, and activates dual pathways (NF-κB via RIP1/TRAF2; apoptosis via FADD/caspase-8), mediating either cell survival or programmed death.

 

Mechanisms of Action of TNF-α in Disease Development

Dysregulated TNF-α is linked to multiple diseases: in rheumatoid arthritis, it induces MMPs to cause cartilage damage; in IBD, it impairs epithelial barrier to exacerbate intestinal inflammation. It also contributes to metabolic diseases by disrupting IRS-1 tyrosine phosphorylation and inducing insulin resistance in obese individuals.

 

Advances in the Development of TNF-α Targeted Drugs

TNF-α plays a central role in inflammatory diseases, leading to the approval of multiple inhibitors. These include monoclonal antibodies (e.g., infliximab, adalimumab) and soluble receptor fusion proteins (e.g., etanercept).

Mechanisms vary: infliximab binds both soluble and transmembrane TNF-α, inducing apoptosis, while etanercept primarily neutralizes soluble TNF-α with lower transmembrane affinity. These differences impact clinical efficacy and safety.

 

Detection Methods

Clinical laboratories primarily use ELISA for quantitative TNF-α detection, recognized as a standard method in the 2021 clinical testing guidelines. TNF-α levels are notably elevated in conditions such as sepsis, cancer, heart failure, and chronic inflammatory diseases.

ELISA operates on antigen-antibody binding, with enzyme-linked secondary antibodies generating colorimetric signals for quantification. Our TNF-α ELISA kit incorporates key innovations: high-affinity monoclonal antibody pairs to prevent cross-reactivity (e.g., with TNF-β), a signal amplification system lowering the detection limit to 5.7 pg/mL, and compatibility with diverse samples including body fluids and tissue homogenates, accompanied by detailed preprocessing protocols.

 

Recommended ELISA products from ELK Biotechnology：

ELK1190  Human TNFa(Tumor Necrosis Factor Alpha) ELISA Kit  

ELK1387 Mouse TNFa(Tumor Necrosis Factor Alpha) ELISA Kit  

ELK1387MS Mouse  (Tumor Necrosis Factor Alpha) Microsample ELISA Kit  

ELK1396  Rat TNFa(Tumor Necrosis Factor Alpha) ELISA Kit  

ELK1164  Rabbit TNFa(Tumor Necrosis Factor Alpha) ELISA Kit  

ELK2216 Cattle TNFa(Tumor Necrosis Factor Alpha) ELISA Kit  

ELK2407  Pig TNFa(Tumor Necrosis Factor Alpha) ELISA Kit  

ELK5364  Chicken TNFa(Tumor Necrosis Factor Alpha) ELISA Kit  

ELK5855  Goat TNFa(Tumor Necrosis Factor Alpha) ELISA Kit  

ELK5856  Horse TNFa(Tumor Necrosis Factor Alpha) ELISA Kit  

ELK8038  Sheep TNFa(Tumor Necrosis Factor Alpha) ELISA Kit  

ELK8512  Zebrafish TNFa(Tumor Necrosis Factor Alpha) ELISA Kit  

ELK1113  Dog TNFa(Tumor Necrosis Factor Alpha) ELISA Kit

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