HMGB1 and related pediatric diseases

Our body has to recognize dangerous stimuli or attaches by pathogens, to limit further damage through the role of immunological mechanisms, to regenerate the damaged tissues, and if possible, to learn from the experience and in particular, be prepared for further encounters with the same or similar pathogens (the role of adaptive immunity). In the signaling system the DAMPs play a key role: they are receptors able to distinguish the self by non-self molecules, specifically recognize structural motifs of molecules known as PAMPs (pathogen associated molecular patterns). Although several endogenous danger signals should exist, and evidence is accumulating about some of them, one of the better known is HMGB1. Infact several cell types appear to be capable of HMGB1 secretion under stress conditions; cells approaching death by lethal irradiation, treatment with specific antitumor drugs, or autophagy also secrete HMGB1 . HMGB1 can be considered as a DAMP (damage-associated molecular pattern molecule): it is a nearly ubiquitous molecule that in physiological conditions is not detectable (it is contained within living cells or is sequestered onto chromatin in apoptotic cells), whereas its presence in the extracellular medium indicates that some cells have died traumatically, are in great distress, or anyway want to alert other cells to immediate danger.