Alarmin(g) news about danger

The EMBO Workshop on Innate Danger Signals and HMGB1 took place between 8 and 11 February 2006 in Milan, Italy, and was organized by M. Bianchi, K. Tracey and U. Andersson.![][1] During evolution, multicellular organisms have developed mechanisms to counteract life‐threatening events, such as infections and tissue injury, as well as to restore tissue homeostasis. These mechanisms are called ‘the inflammatory response‘. To initiate an appropriate inflammatory response, organisms have developed ways to recognize potentially life‐threatening events. Danger signals—the molecules that alert the innate immune system and trigger defensive immune responses—have been classically defined as exogenous, pathogen‐associated molecular pattern (PAMP) molecules. PAMPs—for example, lipopolysacharide (LPS), viral RNA and bacterial petidoglycans—interact with dedicated receptors on immune cells, the so‐called pattern recognition receptors (PRRs). On ligation, PRRs transduce activation signals that lead to the production of proinflammatory molecules such as tumour necrosis factor (TNF). A well‐known family of PRRs is the toll‐like receptor (TLR) family in which each member recognizes a specific set of PAMPs.However, several endogenous molecules also initiate inflammatory responses by interacting with signalling receptors; such innate danger signals are known as endokines and/or alarmins. The term endokine reflects the potential of these molecules with intranuclear and/or intracellular functions also to act extracellularly, in this case to be immunostimulatory on their release from necrotic cells. The endokine family includes high‐mobility‐group box (HMGB) proteins, interleukins such as IL‐1α, cytosolic calcium‐binding proteins of the S100 family, heat‐shock proteins (HSPs) and nucleosomes. The term alarmin, coined by J. Oppenheim (Frederick, MD, USA) and co‐workers, denotes an array of structurally diverse multifunctional host proteins that are rapidly released during infection or tissue damage, and that have mobilizing and activating effects on receptor‐expressing cells engaged in host defence and tissue repair. Innate‐immune mediators that have alarmin function include defensins, eosinophil‐derived neurotoxin, cathelicidins and HMGB1 … [1]: /embed/graphic-1.gif