Browsing by Author "Díaz Pérez, Julio Alexander"

Psoriasis vulgaris is a chronic inflammatory cutaneous disease that affects approximately 2% of the US population. Psoriasis occurs when a genetically susceptible individual has a trigger stimulus that initiates cell selection, proliferation and damage. During the past four decades, predictive gene signatures, important participating cells and specific signaling mediators have been identified. A better understanding of these pathogenic events have lead to more effective, targeted methods to prevent, diagnose and treat this disease. However, more advances are required in early disease. Several triggers have been proposed as initiator events for psoriasis, including alarmins such as ATP. ATP is a particularly interesting alarmin that, via P2X7 receptor (P2X7R) signaling, induces NF-­κB activation and the IL-­23/IL-­17 axis, both of which have been shown to be psoriasis susceptibility pathways. However, the role of alarmins in psoriasis mechanistic pathogenesis have not been well addressed. Here I report that 2’(3’)-­O-­(4-­ Benzoylbenzoyl) adenosine 5’-­triphosphate, an ATP analog and P2X7R agonist, in the presence of an ATPase inhibitor induced psoriasiform dermatitis in mice characterized by acanthosis, increased vascularity, parakeratosis, microabscess formation, and increased inflammation and inflammatory infiltrates. The induced inflammatory response is largely dependent on the IL-­1β/NLRP3 inflammasome pathway and neutrophils extracellular traps. In conclusion, my results demonstrate that cutaneous inflammatory responses induced via alarmin signaling through the P2X7R have implications in the pathogenesis and potential treatment of inflammatory diseases, such as psoriasis.