One of the transcription factors that is activated by TNF-alpha signal transduction pathways is NFkB. NFkB is a transcription factor that helps to express inflammatory genes, resulting in the secretion of various cytokines such as Pro-IL-1 beta and 
TNF-alpha


Tulane University

Proteins produced by cells in response to an infection in order to alert nearby cells of the microbiological threat. Lymphocytes can make cytokines, specifically named lymphokines or interleukins (IL). Cytokines act as ligands and bind to a specific receptor along the plasma membrane to induce an intracellular signaling cascade. A prominent example of cytokines are Type I and Type II Interferons. 

Pro-inflammatory Cytokines

Parham, P. (2009). Vaccination to Prevent Infectious Disease. In 1145902806 862124677 J. Foltin (Ed.), The Immune System (3rd ed., pp. 62-65). New York, New York: Garland Science, Taylor & Francis Group.

The Immune System

Rice GI, Melki I, Frémond ML, Briggs TA, Rodero MP, Kitabayashi N, Oojageer A, Bader-Meunier B, Belot A, Bodemer C, Quartier P, Crow YJ. Assessment of Type I Interferon Signaling in Pediatric Inflammatory Disease. J Clin Immunol. 2017 Feb;37(2):123-132. doi: 10.1007/s10875-016-0359-1. Epub 2016 Dec 9. PMID: 27943079; PMCID: PMC5325846.

Assessment of Type I Interferon Signaling in Pediatric Inflammatory Disease

Type I Interferon is a subset of interferon (IFN) that can be divided into multiple categories. However, rheumatologists generally only consider IFN-Beta and IFN-Alpha, which are transcribed by a family of linked genes on chromosome 9. Disruption to IFN signaling can result in inflammatory and autoimmune disorders, which are at times referred to as type I interferonopathies. Functioning immune systems are characterized by low concentrations of circulating type I IFN and cells with type I IFN receptors. 

Type I Interferon (IFN)

Inflammatory Cytokines are proteins produced by the immune system that induce inflammation. They play a critical role in regulating the body to defend against pathogens.

Inflammatory Cytokines

TNF-alpha is a pro-inflammatory cytokine critical to the innate immune response and is produced by macrophages and monocytes. It increases the permeability of the vascular endothelium, which allows other cells of the immune system (like neutrophils) to travel to the site of infection. Clinical manifestations of this cytokine include prolonged, febrile illnes. TNF-alpha also plays a role in cell apoptosis and necrosis. Additionally, through the induction of a complex cytokine signaling pathway, transcription factors are activated which go on to express inflammatory cytokines. Common treatments for overexpression of TNF-alpha are TNF inhibitors. 


Tumor Necrosis Factor-alpha (TNF-alpha)

NFkB

- Clinical phenotype
- Molecular phenotype
- Function
- Treatment for signaling dysregulation

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