TNF-Tumor Necrosis Factor (Alpha) |Elisa - Clia - Antibody - Protein

Background:

Tumor Necrosis Factor (TNF) is a versatile cytokine involvedl in numerous physiological and pathological processes. It holds a critical role in modulating immune responses, inflammation, and apoptosis. While predominantly produced by activated macrophages, TNF can also originate from various cell types like lymphocytes, mast cells, endothelial cells, and fibroblasts. Two well-known forms of TNF are TNF-alpha and TNF-beta, also referred to as lymphotoxin-alpha. TNF-alpha, being extensively studied, exists in both soluble and membrane-bound forms, both capable of initiating biological responses by binding to their respective receptors. TNF signaling operates through two receptors: TNFR1 and TNFR2. TNFR1 is ubiquitously expressed across cell types, whereas TNFR2 is primarily found in endothelial, epithelial, and certain immune cells. TNFR1 signaling typically triggers pro-inflammatory and apoptotic responses, while TNFR2 signaling exhibits anti-inflammatory properties and fosters cell proliferation. In autoimmune disease treatment, suppressing TNFR1 signaling has proved significant, whereas TNFR2 signaling supports wound healing.The primary function of TNF lies in regulating immune cells. It acts as an endogenous pyrogen, inducing fever, apoptotic cell death, cachexia, and inflammation. Additionally, TNF inhibits tumorigenesis and viral replication, and it responds to sepsis through IL-1 and IL-6-producing cells. Dysregulation of TNF production has been implicated in various human diseases including Alzheimer's disease, cancer, major depression, psoriasis, and inflammatory bowel disease (IBD).

Protein Structure:

• Composition: TNF-α is a transmembrane protein that can be cleaved to form a soluble homotrimer.
• Domains:
• Extracellular Domain: Responsible for receptor binding and signaling.
• Transmembrane Domain: Anchors the protein in the cell membrane.
• Intracellular Domain: Plays a role in signaling within the cell.
• Molecular Weight: The mature form of soluble TNF-α is about 17 kDa, while the transmembrane form is about 26 kDa.

Classification and Subtypes:

• Family: TNF-α is part of the TNF superfamily, which includes other members such as TNF-β (also known as lymphotoxin-alpha).
• Subtypes: There are no distinct subtypes of TNF-α, but it exists in both membrane-bound and soluble forms.

Function and Biological Significance:

• Inflammation: TNF-α is a key mediator of inflammation. It promotes the recruitment of immune cells to sites of infection or injury and stimulates the production of other inflammatory cytokines.
• Cell Death: TNF-α can induce apoptosis (programmed cell death) in certain cells, contributing to its anti-tumor properties.
• Immune Response: It plays a critical role in the regulation of immune responses, helping to coordinate the body's defense against pathogens.
• Fever: TNF-α can act on the hypothalamus to induce fever, which is a common response to infection.
• Metabolism: TNF-α influences lipid metabolism and insulin resistance, which links it to metabolic disorders like obesity and type 2 diabetes.

Interactions:

• Receptors: TNF-α exerts its effects by binding to two specific receptors on cell surfaces:
• TNFR1 (TNF Receptor 1): Present on most cell types and mediates the majority of TNF-α’s effects, including apoptosis and inflammation.
• TNFR2 (TNF Receptor 2): Mainly expressed on immune cells and promotes survival and proliferation signals.
• Signaling Pathways: Upon binding to its receptors, TNF-α activates several signaling pathways, including the NF-κB pathway, which regulates the expression of genes involved in inflammation, immunity, and cell survival.

Clinical Issues:

• Autoimmune Diseases: Overproduction of TNF-α is implicated in several autoimmune diseases, such as rheumatoid arthritis, inflammatory bowel disease, and psoriasis. TNF inhibitors are used as treatments for these conditions.
• Cancer: While TNF-α can promote tumor necrosis, chronic inflammation mediated by TNF-α can also contribute to cancer development by creating a tumor-promoting environment.
• Sepsis: High levels of TNF-α are associated with septic shock, a severe systemic inflammatory response to infection that can be life-threatening.
• Cardiovascular Diseases: TNF-α is involved in the pathogenesis of cardiovascular diseases, including atherosclerosis, by promoting inflammation within blood vessels.

Summary:

TNF-α (Tumor Necrosis Factor-alpha) is a pivotal cytokine in the regulation of immune responses and inflammation. It has a dual role in both promoting cell death and survival, depending on the context. TNF-α is crucial in the body's defense against infections and in the development of inflammatory and autoimmune diseases. Understanding TNF-α's functions and mechanisms has led to the development of targeted therapies, such as TNF inhibitors, which are used to treat various inflammatory and autoimmune conditions. However, its role in chronic inflammation also links it to the progression of diseases like cancer and cardiovascular disorders.