Cytokines

Key Biological Properties:

• Molecular Weight: TNF-α is a 17 kDa protein, while TNF-β is slightly larger.
• Structure: TNF-α is a trimeric protein, meaning it forms a complex of three identical subunits.

Expression Patterns:

• TNF-α: Expressed primarily by macrophages, but also by other immune cells such as T cells and natural killer cells.
• TNF-β: Expressed by activated lymphocytes.

Tissue Distribution:

• TNF is found in various tissues, including the spleen, liver, and adipose tissue. It is also present in the bloodstream during systemic inflammation.

Primary Biological Functions:

• Inflammation: TNF is a key mediator of inflammation, promoting the recruitment of immune cells to sites of infection or injury.
• Cell Death: TNF can induce apoptosis (programmed cell death) in certain cells, which is crucial for controlling infections and preventing cancer.
• Immune Response: TNF plays a role in the activation and differentiation of immune cells, enhancing the body’s ability to fight off pathogens.

Role in Immune Responses:

• Pathogen Recognition: TNF helps in recognizing and responding to pathogens by activating immune cells and promoting the production of other cytokines.

Mechanisms with Other Molecules and Cells:

• Receptors: TNF exerts its effects by binding to two receptors, TNFR1 and TNFR2, which are present on the surface of various cells.
• Binding Partners: TNF can interact with other cytokines and signaling molecules to amplify or modulate its effects.

Downstream Signaling Cascades:

• NF-κB Pathway: Activation of TNFR1 leads to the activation of the NF-κB pathway, which promotes the expression of genes involved in inflammation and cell survival.
• MAPK Pathway: TNF can also activate the MAPK pathway, leading to the production of inflammatory mediators.

Regulatory Mechanisms:

• Transcriptional Regulation: The expression of TNF is tightly regulated at the transcriptional level by various transcription factors, including NF-κB and AP-1.
• Post-Translational Modifications: TNF undergoes several post-translational modifications, such as glycosylation and cleavage, which can affect its activity and stability.

Biomedical Research:

• Disease Models: TNF is used in research to study inflammatory diseases, cancer, and autoimmune disorders.

Diagnostic Tools:

• Biomarkers: Elevated levels of TNF in the blood can serve as biomarkers for various inflammatory and autoimmune diseases.

Therapeutic Strategies:

• Anti-TNF Therapies: Drugs that inhibit TNF, such as infliximab and etanercept, are used to treat conditions like rheumatoid arthritis, Crohn’s disease, and psoriasis.

Role Throughout the Life Cycle:

• Development: TNF is involved in embryonic development, particularly in the formation of the immune system.
• Aging: TNF levels can increase with age, contributing to age-related inflammation and diseases.
• Disease: Dysregulation of TNF is associated with various diseases, including chronic inflammatory conditions, cancer, and neurodegenerative disorders.