Tumour necrosis factor’s role in inflammation
Inflammation is a term which you will probably have heard of and most likely experienced its effects; such as the swelling of a twisted ankle or the red skin around a scrape. Inflammation is part of our protective immunological response and the action of our innate immune system, forming the body’s first line of defence.
The inflammatory system is very quick to activate, a trade-off as it is unfortunately not specific and sometimes healthy tissues can get caught up in the crossfire. It is not a problem when inflammation remains localised, for example in a wound. However, when inflammation becomes body-wide, such as in the context of persistent infection, hormone imbalance or in response to pro-inflammatory diets, the process may be more subtle and healthy tissue gets attacked throughout the body which can contribute to chronic health conditions.
This inflammatory mechanism is partly mediated by the switching on of a pro-inflammatory signalling cascade where key genes are activated encoding for inflammatory mediators and enzymes. One of these genes is Tumour Necrosis Factor-alpha (TNF-alpha), a macrophage-derived pro-inflammatory cytokine, which has been associated with a variety of immune-mediated inflammatory conditions.
TNF and gene expression
The activation of genes including pro-inflammatory cytokines is regulated by transcription factor proteins which bind to regions of our DNA genetic code and enable them to be ‘switched on’. Several genetic variants of one such region of the TNF-alpha gene promoter have been reported. The -308G>A variant influences the TNF-alpha gene by increasing the production of this pro-inflammatory cytokine. Therefore, those carrying this genetic variant have an increased ability for transcription factors to ‘switch on’ production of the TNF-alpha gene, increasing the amount of TNF-alpha protein production.
Although the mechanism remains partly obscured, the TNF-alpha 308 genetic variation has been associated with risk of various inflammatory related conditions such as chronic heart disease, type 2 Diabetes Mellitus (T2DM), metabolic syndrome and obesity. It is thought that changes to expression of TNF-alpha i.e. when it is not “switched off”, may contribute to the inflammatory response continuing inappropriately.
So what anti-inflammatory nutrient and lifestyle protocols could potentially help?
Firstly, if a person is symptomatic then have a look at what else could be contributing to their inflammation. The genetic players in inflammation are only part of the picture. It is also important to assess diet, lifestyle and environment factors which may be precipitating an inflammatory response regardless of the genetic variants.
In the case of TNF genetic variants, research is showing potentially beneficially regulatory actions of omega- 3 polyunsaturated fatty acids and green tea extracts in animal models and increasingly in some inflammatory related conditions such as T2DM. Therefore, diet and lifestyle changes which include consuming optimally balanced polyunsaturated fats and epigallocatechin gallate (EGCG) found in green tea may be beneficial and warranted.
Author: myDNAhealth’s scientific officer, Dr Eve Pearce PhD (Medicine), DipION, mBANT, CNHC
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