response to tumor necrosis factor

Definition

Target type: biologicalprocess

Any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a tumor necrosis factor stimulus. [GOC:mah]

Tumor necrosis factor (TNF) is a potent cytokine that plays a central role in inflammation, immune responses, and cell death. TNF is produced mainly by macrophages and T lymphocytes in response to various stimuli, including bacterial and viral infections, inflammatory mediators, and tissue injury. Upon binding to its receptors, TNF initiates a complex signaling cascade that leads to a wide range of cellular responses. These responses can be broadly categorized into:

1. **Survival and Proliferation:** TNF can promote cell survival and proliferation in certain cell types, such as fibroblasts and epithelial cells. This effect is mediated by the activation of the nuclear factor-κB (NF-κB) pathway. NF-κB is a transcription factor that regulates the expression of genes involved in cell survival, inflammation, and immune responses. TNF-induced activation of NF-κB leads to the production of anti-apoptotic proteins and pro-inflammatory cytokines, which help to protect cells from death and promote tissue repair.

2. **Inflammation:** TNF is a key mediator of inflammation. It triggers the release of other pro-inflammatory cytokines, such as interleukin-1 (IL-1) and interleukin-6 (IL-6), and chemokines, which attract immune cells to the site of inflammation. TNF also increases the expression of adhesion molecules on endothelial cells, which facilitates the recruitment of immune cells from the bloodstream into the inflamed tissue. This process is essential for the clearance of pathogens and the repair of damaged tissues.

3. **Apoptosis:** TNF can also induce apoptosis, or programmed cell death, in certain cell types. This effect is mediated by the activation of the caspase cascade. Caspases are a family of proteases that cleave specific proteins, leading to the dismantling of the cell. TNF-induced apoptosis is a crucial mechanism for eliminating infected cells and cancer cells, and for maintaining tissue homeostasis.

4. **Other responses:** TNF also plays a role in other biological processes, such as angiogenesis (new blood vessel formation), bone resorption, and energy metabolism. These responses are mediated by the activation of various signaling pathways downstream of the TNF receptors.

The biological response to TNF is tightly regulated by a complex network of factors. These factors include:

* **TNF receptors:** TNF exerts its effects by binding to two distinct receptors: TNFR1 (also known as p55) and TNFR2 (also known as p75). TNFR1 is the primary mediator of TNF-induced apoptosis, while TNFR2 is involved in survival and proliferation.

* **Signaling molecules:** TNF receptors activate a cascade of signaling molecules, including adaptor proteins, kinases, and transcription factors. The specific signaling pathways activated by TNF depend on the cell type and the context.

* **Regulatory proteins:** A variety of regulatory proteins control the activity of TNF and its receptors. These proteins include inhibitors of TNF signaling, such as TNFα-binding protein (TNFα-BP) and soluble TNFRs, and activators of TNF signaling, such as TNF-converting enzyme (TACE).

The biological response to TNF is highly context-dependent. In some situations, TNF can be beneficial, such as in the clearance of pathogens and the repair of damaged tissues. However, in other situations, TNF can be detrimental, such as in the development of chronic inflammatory diseases and autoimmune disorders. Therefore, the regulation of TNF signaling is crucial for maintaining health and preventing disease.'
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Proteins (16)

Compounds (618)