A place for TACE: inhibition of tumour necrosis factor [alpha] converting enzyme as a new therapeutic target in inflammatory bowel disease. (Commentaries).(TNF-[alpha] converting enzyme)

Vertebrates, and humans are no exception, have developed potent innate and adaptive immune systems that deal with potential lethal encounters with microorganisms, which are critically dependent on the biological effects of proinflammatory cytokines such as interleukin 12, interleukin 18, interferon [gamma], and tumour necrosis factor [alpha] (TNF-[alpha]). The pivotal role of these cytokines is underscored by the observation that neutralisation of TNF-[alpha] in patients with Crohn's disease may convert latent tuberculosis into a potentially lethal disseminated form. (1) Thus proinflammatory cytokines are necessary for survival of the human species, but as they may cause significant inflammatory damage, their production and secretion need to be tightly regulated.

Indeed, the production and secretion of TNF-[alpha] are controlled at multiple checkpoints, no doubt in order to prevent unrestrained inflammation and tissue damage. TNF-[alpha] is translated as a precursor protein which contains an unusually long signal peptide that anchors the protein to the outer membrane. During local and systemic inflammatory reactions, membrane bound TNF-[alpha] is cleaved extracellularly by a specific zinc dependent metalloprotease that has …