role of damage-associated molecular patterns in human diseases: part I - promoting inflammation and immunity

There is increasing interest by physicians in the impact of the innate immune system on human diseases. In particular, the role of the molecules that initiate and amplify innate immune pathways, namely damage-associated molecular patterns [DAMPs], is of interest as these molecules are involved in the pathogenesis of many human disorders. The first part of this review identifies five classes of cell stress/tissue injury-induced DAMPs that are sensed by various recognition receptor-bearing cells of the innate immune system, thereby mounting inflammation, promoting apoptosis and shaping adaptive immune responses. The DAMPs activate and orchestrate several innate immune machineries, including inflammasomes and the unfolded protein response that synergistically operates to induce inflammatory, metabolic and adaptive immune pathologies. Two examples of autoimmune diseases are discussed as they represent a typical paradigm of the intimate interplay between innate and adaptive immune responses

role of damage-associated molecular patterns [DAMPs] in human diseases part II: DAMPs as diagnostics, prognostics and therapeutics in clinical medicine

This article is the second part of a review that addresses the role of damage-associated molecular patterns [DAMPs] in human diseases by presenting examples of traumatic [systemic inflammatory response syndrome], cardiovascular [myocardial infarction], metabolic [type 2 diabetes mellitus], neurodegenerative [Alzheimer's disease], malignant and infectious diseases. Various DAMPs are involved in the pathogenesis of all these diseases as they activate innate immune machineries including the unfolded protein response and inflammasomes. These subsequently promote sterile autoinflammation accompanied, at least in part, by subsequent adaptive autoimmune processes. This review article discusses the future role of DAMPs in routine practical medicine by highlighting the possibility of harnessing and deploying DAMPs either as biomarkers for the appropriate diagnosis and prognosis of diseases, as therapeutics in the treatment of tumours or as vaccine adjuncts for the prophylaxis of infections. In addition, this article examines the potential for developing strategies aimed at mitigating DAMPs-mediated hyperinflammatory responses, such as those seen in systemic inflammatory response syndrome associated with multiple organ failure