TNF Full Form

Since its discovery, TNF has been the focus of research for its functions in normal physiology, acute inflammation, chronic inflammation, autoimmune illness, and cancer-related inflammation. In addition, TNF receptor 1 (TNFR1)-mediated apoptosis, necrosis (also known as necroptosis) and survival in TNF signalling have also received a lot of studies, resulting in a lot of novel results and hypotheses. This mini-review covers the discovery and definition of TNF and its origins, biological and pathological activities, and molecular mechanisms of action.

TNF Full Form

TNF stands for Tumor necrosis factor. Tumor necrosis factor (TNF) is a cytokine generated by immune cells that can limit tumour cell growth and cause tumour regression. It was discovered in the late 1970s. TNF is a 157-amino-acid protein produced as a membrane-bound protein (pro-TNF) and released by cleavage by the TNF-converting enzyme (TACE). TNF has been implicated in several physiological and pathological reactions, including inflammation, tumour growth, transplant rejection, rheumatoid arthritis, and septic shock since it was cloned in 1984.

Discovery

Dr Williams B. Coley employed crude bacterial preparations to treat tumour patients more than a century ago. He discovered that the bacterial extracts might cause tumour necrosis. While tumours regressed, those who received bacterial extracts experienced a significant systemic inflammatory response. One of the essential inflammatory stimulators presently known to trigger this reaction was discovered in 1975, when a protein factor detected in the serum of endotoxin-treated mice caused lysis in tumour cells, earning it the label “tumour necrosis factor.” The TNF gene was identified and described in 1984. Around the same time, another gene encoding a protein was identified and described, extracted from T lymphocytes and termed T lymphotoxin alpha in 1968. These two genes were discovered to be members of the same gene family. TNF was therefore called “TNFα,” whereas TLα was called “TNFβ.” Dr Bruce Beutler, a Nobel Laureate, and his colleagues isolated cachectin from the supernatant of endotoxin-treated macrophages in 1985. This protein caused wasting (cachexia) and septic shock in mouse recipients. TNF and cachectin were eventually shown to be the same protein.

Genes and Proteins

The TNF genes are found on chromosomes 6 and 17 in humans and mice, respectively, preceded by the TNFβ gene. Both genes are present in a single copy, are three kilobases in length, and have four exons. Within the promoter region of the TNF gene, many DNA binding sites for the transcription factor nuclear factor kappa B (NF-κB) have been found; hence, TNFα expression appears to be NF-κB dependent. In addition, the promoter region of the TNF gene has a DNA binding site for the high mobility group 1 (HMG1) protein.

TNFα comes in two forms: membrane-bound (mTNFα) and soluble (sTNFα). Human mTNαF has 157 amino acids and a 76-aa leader sequence, whereas mouse mTNF has 156 amino acids and a 79-aa leader sequence. TNFα translocates to the cell membrane during production, where the TNFα converting enzyme (TACE) converts mTNFα to sTNFα. In contrast to TNFα, TNFβ, on the other hand, only occurs in a soluble form (sTNFβ). TNF is found in all living things. Human TNF, for example, is 80% identical to mouse TNF. TNFα and TNFβ have roughly 30% homology in both species.

Biological and Pathological Functions

TNF has several physiological and clinical effects. TNF promotes necrosis and apoptosis in tumour cells. TNF is also critical for lymph node follicle and germinal centre production, as well as host defence against bacterial and viral infection, according to research conducted in TNF- or TNFR-deficient mice. TNF has been identified as a fever-causing endogenous pyrogen. Cachexia, wasting syndrome, and depression may result from chronic low-dose TNF exposure.

TNF is also an essential mediator of both acute and chronic inflammatory processes. TNF increases the synthesis of additional inflammatory cytokines and chemokines in addition to its release. TNF has a crucial role in endotoxin-induced septic shock in animals and chemotherapy-induced septic shock in late-stage lung cancer patients. In addition, TNF is involved in rheumatoid arthritis (RA), inflammatory bowel illnesses such as Crohn’s disease and ulcerative colitis, multiple sclerosis, systemic lupus erythematosus, and systemic sclerosis.

Finally, carcinogenesis, tumour development, invasion, and metastasis all have TNF risk factors. TNF is an essential mediator in cancer-related chronic inflammation. Long-term aspirin use reduces TNF release and lowers the risk of human colorectal colon cancer. TNF is also often found in human breast, ovarian, and kidney cancer biopsy samples and neighbouring stromal cells.

Conclusion

TNF is a key pro-inflammatory cytokine involved in the pathophysiology of immunological diseases and tumour growth. The development of a new generation of anti-TNF medicines with fewer side effects and high efficacy in the treatment of immunological diseases and cancer-related inflammation will be aided by a better knowledge of TNF’s activities and the processes behind TNF pathology.