NF-kB is the master regulator – the primary means by which inflammation is ‘adjusted’ – turned on and off. Many, many different molecules interact with NF-kB – some stimulating it (increasing inflammation) and others inhibiting it (decreasing inflammation.) The balance between these positive and negative forces determines the extent of inflammation at any given time.
However, the system is not ’static.’ Various products of inflammation can stimulate further inflammation – or they may inhibit further inflammation. When the products of inflammation inhibit further inflammation, that is a negative feedback loop. Without these negative feedback loops, or with dysfunctional or poorly functioning negative feedback loops, it is difficult to stop inflammation once it gets started.
TNFAIP3 is a key player in some of these negative feedback loops. it’s important. Without properly functioning TNFAIP3, NF-kB might remain set in the “more inflammation” position.
In the study referenced below, researchers found a mutation at the genetic site controlling TNFAIP3. That genetic mutation is associated with Crohn’s disease, rheumatoid arthritis, systemic lupus erythematosus, psoriasis, type 1 diabetes and other inflammation related disease conditions.
This indicates the importance of TNFAIP3.
It also indicates the importance of NF-kB as the master switch.
It also suggests yet another possible reason why those with one inflammation related condition are more likely to have others as well.
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The ubiquitin-editing enzyme A20 (TNFAIP3) is a central regulator of immunopathology.
Vereecke L, Beyaert R, van Loo G.
Department for Molecular Biomedical Research, Unit of Molecular Signal Transduction in Inflammation, VIB, Ghent B-9052, Belgium.
Nuclear factor (NF)-kappaB has an important role in immunity and inappropriate NF-kappaB activity has been linked with many autoimmune and inflammatory diseases. Multiple mechanisms normally ensure the proper termination of NF-kappaB activation. TNFAIP3 is a key player in the negative feedback regulation of NF-kappaB signaling in response to multiple stimuli. Moreover, TNFAIP3 also regulates tumor necrosis factor (TNF)-induced apoptosis. Recent genetic studies demonstrate a clear association between several mutations in the human TNFAIP3 locus and immunopathologies such as Crohn’s disease, rheumatoid arthritis, systemic lupus erythematosus, psoriasis and type 1 diabetes. These findings further illustrate the importance of A20 in the resolution of inflammation and the prevention of human disease.
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