Tumor necrosis factor: Difference between revisions

Latest revision as of 04:49, 18 February 2025

Tumor Necrosis Factor[edit]

Tumor Necrosis Factor (TNF) is a cytokine involved in systemic inflammation and is part of the body's immune response. It is produced chiefly by activated macrophages, although it can be produced by other cell types such as lymphocytes, fibroblasts, and neurons. TNF is a member of a group of cytokines that stimulate the acute phase reaction.

Structure[edit]

TNF is a trimeric protein, meaning it is composed of three identical subunits. Each subunit is a monomer that binds to the others to form the active cytokine. The TNF monomer is a compact, globular protein with a characteristic fold that is shared among members of the TNF superfamily.

Function[edit]

TNF plays a key role in regulating immune cells. It is able to induce fever, apoptosis (programmed cell death), cachexia (wasting syndrome), and inflammation. TNF is also involved in the regulation of cellular proliferation, differentiation, and death. It is a critical component of the inflammatory response and is involved in the pathogenesis of various diseases, including rheumatoid arthritis, inflammatory bowel disease, and psoriasis.

Receptors[edit]

TNF exerts its effects by binding to its receptors, TNFR1 and TNFR2.

TNFR1[edit]

TNFR1 is ubiquitously expressed and can be activated by both the membrane-bound and soluble forms of TNF. Upon activation, TNFR1 can initiate several signaling pathways, including the activation of NF-_B, which leads to the expression of genes involved in inflammation and survival.

TNFR2[edit]

TNFR2 is primarily expressed in immune cells and is activated mainly by the membrane-bound form of TNF. TNFR2 signaling is associated with the activation of anti-apoptotic pathways and the promotion of cell survival and proliferation.

Clinical Significance[edit]

Due to its role in inflammation and immune regulation, TNF is a target for therapeutic intervention in various inflammatory diseases. TNF inhibitors, such as infliximab, etanercept, and adalimumab, are used to treat conditions like rheumatoid arthritis, ankylosing spondylitis, and Crohn's disease. These inhibitors work by blocking the interaction of TNF with its receptors, thereby reducing inflammation and tissue damage.

Related Pages[edit]

References[edit]

Aggarwal, B. B., & Natarajan, K. (1996). Tumor necrosis factors: Developments during the last decade. European Cytokine Network, 7(2), 93-124.
Balkwill, F. (2009). Tumour necrosis factor and cancer. Nature Reviews Cancer, 9(5), 361-371.

Tumor_necrosis_factor[edit]

Enhanceosome composition of human TNF
TNF Exons and Introns
TNF Monomer
TNFR1 Cell Signaling
TNFR2 Cell Signaling

@@ Line 1: / Line 1: @@
 == Tumor Necrosis Factor ==
-'''Tumor necrosis factor''' (often abbreviated as '''TNF''') is a cell signaling protein involved in systemic inflammation and belongs to a group of cytokines. It is primarily recognized as a biological response modifier, a substance that has the potential to enhance the body's natural defense mechanisms against diseases, including cancer. The role of TNF in inducing cell death in cancer cells is a major area of research, and while its exact mechanisms are not entirely understood, its significance in the immune response is well-established.
+[[File:Enhanceosome_composition_of_human_TNF.svg|thumb|right|Enhanceosome composition of human TNF.]]
+[[File:TNF_Exons_and_Introns.svg|thumb|right|Diagram of TNF exons and introns.]]
-=== Overview ===
+'''Tumor Necrosis Factor''' ('''TNF''') is a [[cytokine]] involved in systemic inflammation and is part of the body's [[immune response]]. It is produced chiefly by activated [[macrophages]], although it can be produced by other cell types such as [[lymphocytes]], [[fibroblasts]], and [[neurons]]. TNF is a member of a group of cytokines that stimulate the acute phase reaction.
-TNF is produced primarily by activated macrophages, but it is also produced by various other cell types including lymphoid cells. This protein plays a pivotal role in regulating diverse cell activities like cell survival, proliferation, differentiation, and death.
+== Structure ==
-=== Role in Cell Death ===
+[[File:TNFMonomer.png|thumb|right|Structure of a TNF monomer.]]
+TNF is a trimeric protein, meaning it is composed of three identical subunits. Each subunit is a monomer that binds to the others to form the active cytokine. The TNF monomer is a compact, globular protein with a characteristic fold that is shared among members of the TNF superfamily.
-TNF can induce a variety of intracellular signaling pathways including inflammation, cell survival, and cell death. When it comes to cancer, TNF has gained attention for its ability to cause necrosis or death of tumor cells. However, the exact mechanism by which TNF promotes cancer cell death remains a subject of intense investigation.
+== Function ==
-==== Mechanisms Under Investigation ====
+TNF plays a key role in regulating immune cells. It is able to induce [[fever]], [[apoptosis]] (programmed cell death), [[cachexia]] (wasting syndrome), and inflammation. TNF is also involved in the regulation of [[cellular proliferation]], differentiation, and death. It is a critical component of the inflammatory response and is involved in the pathogenesis of various diseases, including [[rheumatoid arthritis]], [[inflammatory bowel disease]], and [[psoriasis]].
-* '''Apoptosis''': Some studies suggest that TNF can initiate the apoptotic cell death pathway in certain cells, leading to the systematic death of these cells without causing inflammation.
+== Receptors ==
-* '''Necroptosis''': A regulated form of necrosis, necroptosis can be induced by TNF in certain circumstances. This form of cell death is inflammatory and might have implications in various diseases, including cancer.
-=== Clinical Implications ===
+TNF exerts its effects by binding to its receptors, [[TNFR1]] and [[TNFR2]].
-The therapeutic potential of TNF has led to the exploration of its use in cancer treatment. Understanding how TNF interacts with cancer cells can pave the way for innovative treatments that can either boost or inhibit its activity, depending on the therapeutic goal.
+=== TNFR1 ===
-=== Current Research ===
+[[File:TNFR1_Cell_Signaling.svg|thumb|right|TNFR1 cell signaling pathway.]]
+TNFR1 is ubiquitously expressed and can be activated by both the membrane-bound and soluble forms of TNF. Upon activation, TNFR1 can initiate several signaling pathways, including the activation of [[NF-_B]], which leads to the expression of genes involved in inflammation and survival.
-As of now, research on TNF is multi-faceted. While its role as a biological response modifier is clear, its diverse cellular effects, ranging from promoting inflammation to causing cell death, make it a complex molecule to study. Ongoing investigations aim to elucidate the exact pathways through which TNF acts and to harness its potential for therapeutic purposes.
+=== TNFR2 ===
-== See Also ==
+[[File:TNFR2_cell_signaling.svg|thumb|right|TNFR2 cell signaling pathway.]]
-* [[Cytokines]]
+TNFR2 is primarily expressed in immune cells and is activated mainly by the membrane-bound form of TNF. TNFR2 signaling is associated with the activation of [[anti-apoptotic]] pathways and the promotion of cell survival and proliferation.
+== Clinical Significance ==
+Due to its role in inflammation and immune regulation, TNF is a target for therapeutic intervention in various inflammatory diseases. [[TNF inhibitors]], such as [[infliximab]], [[etanercept]], and [[adalimumab]], are used to treat conditions like rheumatoid arthritis, [[ankylosing spondylitis]], and [[Crohn's disease]]. These inhibitors work by blocking the interaction of TNF with its receptors, thereby reducing inflammation and tissue damage.
+== Related Pages ==
+* [[Cytokine]]
+* [[Inflammation]]
+* [[Rheumatoid arthritis]]
 * [[Apoptosis]]
-* [[Necroptosis]]
-* [[Biological response modifiers]]
+== References ==
-* [[Cancer therapy]]
+* Aggarwal, B. B., & Natarajan, K. (1996). Tumor necrosis factors: Developments during the last decade. European Cytokine Network, 7(2), 93-124.
-{{stub}}
+* Balkwill, F. (2009). Tumour necrosis factor and cancer. Nature Reviews Cancer, 9(5), 361-371.
-{{PDB_Gallery|geneid=7124}}
-{{Cytokines}}
+[[Category:Immunology]]
-{{TNF receptor superfamily modulators}}
-{{Portal bar|Biology|Medicine}}
 [[Category:Cytokines]]
-[[Category:Immunostimulants]]
+== Tumor_necrosis_factor ==
+<gallery>
+File:Enhanceosome_composition_of_human_TNF.svg|Enhanceosome composition of human TNF
+File:TNF_Exons_and_Introns.svg|TNF Exons and Introns
+File:TNFMonomer.png|TNF Monomer
+File:TNFR1_Cell_Signaling.svg|TNFR1 Cell Signaling
+File:TNFR2_cell_signaling.svg|TNFR2 Cell Signaling
+</gallery>