090 Inhibition of HMGB1 attenuates the inflammatory response in keratinocytes

Recessive dystrophic epidermolysis bullosa (RDEB) is a blistering skin disease caused by mutations in COL7A1, the gene encoding type VII collagen (C7). RDEB characterized chronic wounds and high incidence of aggressive squamous cell carcinoma (SCC), leading cause death this patient population. High mobility group box 1 (HMGB1) serum biomarker severity patients that may have mechanistic role promoting SCC carcinogenesis. HMGB1 chromatin-associated protein has dual as mediator DNA repair nucleus damage-associated molecular pattern stimulates innate immune response when secreted extracellularly to inflammatory stimuli or cellular damage. We hypothesize nuclear depletion excessive secretion drives carcinogenesis positive feedback loop further exacerbates inflammation genomic instability. Inhibition using small molecule drug, inflachromene, keratinocytes stimulated with lipopolysaccharide results 5-fold reduction pro-inflammatory cytokine IL-6 (p < 0.0001). conclude inhibiton attenuates warrants study determine whether potential therapeutic target SCC. Future directions are aimed at interrogating keratinocyte damaging agents (psoralen, cisplatin, γ-irradiation UV-B radiation) presence absence inhibitor. Additionally, we generated an vitro model CRISPR/Cas9 gene-editing knock out C7 immortalized lines will be used elucidate effects inhibition keratinocytes.