Tumour Necrosis Factor Alpha Case Study

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Tumour necrosis factor-alpha (TNFa) is a pro-inflammatory monocyte derived cytokine identified as initiating a number of crucial cell mechanisms, largely within the regulation of immune cells and host defence. It is secreted primarily by macrophages and monocytes in response to a bacterial challenge or tumour. Although TNFa is mainly produced by macrophages, it is also produced by a broad variety of other tissues including (but not limited to) endothelial cells, mast cells, fibroblasts and lymphoid cells.
TNFa is an endogenous pyrogen, thus is capable of inducing inflammation, fever, apoptotic cell death and, inhibition of tumorigenesis. (Kleef and Hager, 2000) One of the most potent stimuli for TNFa is a bacterial endotoxin (lipopolysaccharide) or (LPS) which is derived from the outer cell wall of gram-negative bacteria. (Verhoef et al., 1999) LPS is a major component of the outer membrane of gram-negative bacteria, and contributes greatly to the structural integrity of the bacteria. (Kaszowska, 2004) Large amounts of TNFa are released in …show more content…

These cells are present as monocytes within original culture, however were differentiated to form macrophage cells using PMA, a plant ester (and toxin) which is used in many cell models. PMA produces macrophages from the monocytic U937, through the promotion and activation of protein kinase C. PMA is detected by tyrosine kinase receptors found upon the surface of monocytic cells and initiates a cascade of changes within the U937 cells. The activation of Phospholipase C is a crucial change within the monocytic cell as this in turn activates diacylglycerol, which results in the activation of Protein Kinase C. This PKC molecule will be transported to the nucleus where it will initiate the differentiation process. (Vrana and Grant, 2001), (Signal transduction, no

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