Danger-Associated Molecular Patterns (DAMPs): the Derivatives and Triggers of Inflammation.

PURPOSE OF REVIEW: Allergen is an umbrella term for irritants of diverse origin. Along with other offenders such as pathogens, mutagens, xenobiotics, and pollutants, allergens can be grouped as inflammatory agents. Danger-associated molecular patterns (DAMPs) are altered metabolism products of necrotic or stressed cells, which are deemed as alarm signals by the innate immune system. Like inflammation, DAMPs play a role in correcting the altered physiological state, but in excess, they can be lethal due to their signal transduction roles. In a vicious loop, inflammatory agents are DAMP generators and DAMPs create a pro-inflammatory state. Only a handful of DAMPs such as uric acid, mtDNA, extracellular ATP, HSPs, amyloid β, S100, HMGB1, and ECM proteins have been studied till now. A large number of DAMPs are still obscure, in need to be unveiled. The identification and functional characterization of those DAMPs in inflammation pathways can be insightful.

RECENT FINDINGS: As inflammation and immune activation have been implicated in almost all pathologies, studies on them have been intensified in recent times. Consequently, the pathologic mechanisms of various DAMPs have emerged. Following PRR ligation, the activation of inflammasome, MAPK, and NF-kB is some of the common pathways. The limited number of recognized DAMPs are only a fraction of the vast array of other DAMPs. In fact, any misplaced or abnormal level of metabolite can be a DAMP. Sophisticated analysis studies can reveal the full profile of the DAMPs. Lowering the level of DAMPs is useful therapeutic intervention but certainly not as effective as avoiding the DAMP generators, i.e., the inflammatory agents. So, rather than mitigating DAMPs, efforts should be focused on the elimination of inflammatory agents.