090 Inhibition of HMGB1 attenuates the inflammatory response in keratinocytes

Abstract

Recessive dystrophic epidermolysis bullosa (RDEB) is a blistering skin disease caused by mutations in COL7A1, the gene encoding type VII collagen (C7). RDEB is characterized by chronic wounds and a high incidence of aggressive squamous cell carcinoma (SCC), the leading cause of death in this patient population. High mobility group box 1 (HMGB1) is a serum biomarker of disease severity in RDEB patients that may have a mechanistic role in promoting SCC carcinogenesis. HMGB1 is a chromatin-associated protein that has a dual role as a mediator of DNA repair in the nucleus and a damage-associated molecular pattern that stimulates the innate immune response when secreted extracellularly in response to inflammatory stimuli or cellular damage.