Damage-associated molecular patterns (DAMPs) are endogenous molecules released by stressed or dying cells that signal tissue damage and initiate an inflammatory response. Unlike pathogen-associated molecular patterns (PAMPs), which originate from pathogens, DAMPs are produced by the body's own cells, indicating cellular injury or stress rather than infection.
Common DAMPs include high mobility group box 1 (HMGB1), ATP, uric acid, heat shock proteins, and DNA fragments. These molecules are typically contained within cells but are released into the extracellular space during cell damage or death. Once released, DAMPs are recognized by pattern recognition receptors (PRRs) such as Toll-like receptors (TLRs) and NOD-like receptors (NLRs) on immune cells.
The binding of DAMPs to PRRs triggers intracellular signaling pathways that lead to the production of pro-inflammatory cytokines and chemokines. This, in turn, recruits and activates immune cells to the site of damage, promoting the clearance of dead cells and debris and initiating tissue repair processes. For example, ATP released from damaged cells can activate the NLRP3 inflammasome, leading to the production of interleukin-1β (IL-1β), a key mediator of inflammation.
While the inflammatory response induced by DAMPs is crucial for healing and maintaining tissue homeostasis, excessive or chronic release of DAMPs can contribute to persistent inflammation and the development of various diseases, including autoimmune disorders, chronic inflammatory conditions, and cancer.