[Calpains participate in inflammatory reaction development]

Abstract

Calpains are cysteine proteases first identified 50 years ago. Because they are present in the cytosol of mammalian cells and because they are activated in response to Ca2+ mobilization, they are thought to be involved mainly in cell signalling pathways. They could participate in cellular responses such as apoptosis, proliferation, extracellular matrix adhesion and motility, that have relevance to pathophysiological issues in ischemia, inflammation, repair and tumor progression. Here we consider calpain functions in inflammatory reaction. We report the recent observation that calpain inhibitors reduce the development of acute and chronic inflammation. This has opened the door for understanding how these enzymes are effective in inflammation. We present data suggesting that calpains are primarily responsible for the activation of nuclear factor-kappa B, a transcription factor with a pivotal role in inflammation. They are involved in inflammatory cell adhesion and migration, pro-inflammatory mediator release and anti-inflammatory hormone resistance as well. In addition, we emphasize the intriguing possibility that calpains are externalized during inflammatory process and that they play a role in the microenvironment of inflammatory cells. Thus, both intracellular and extracellular calpains would offer novel therapeutic targets in inflammation.