TNF is a pleiotropic cytokine that can elicit a wide range of cellular
responses. It is a major mediator of apoptosis as well as of inflammation
and immunity. TNF has been implicated in the pathogenesis of a wide
spectrum of human diseases, including sepsis, diabetes, cancer, osteoporosis,
multiple sclerosis, rheumatoid arthritis, and inflammatory bowel diseases.
The wide range of biological responds derives from the interaction
of TNF with its two receptors TNFR1 and TNFR2, that initiate several
intracellular signal transductionpathways. The apoptotic pathway
engages so-called caspases and finally leads to programmed cell death,
where the single cell is killed (programmed to undergo suicide) for the
benefit of the organism. The NF-kB pathway activated by TNF counteracts
apoptosis by inducing anti-apoptotic molecules. Although many components
of the TNF signaling pathways have been identified, the complex network
of interacting signals leading to the decision between cellular life and
death is still poorly understood. NF-kB is also responsible for the inflammation
responses, and the role of the JNK pathway remains elusive. A short introduction
to TNF is provided by a recent short review (download) and an extended introduction to
TNF as well as an introduction to molecular biology is available upon request.