ADAM10 inhibits the interaction between IL-17 and HMGB1 in Buerger's disease

OBJECTIVE: Buerger's disease is a rare disease that causes critical limb ischemia: however, the underlying pathophysiological mechanism remains unclear. Therefore, we investigated the interaction between interleukin (IL)-17 and high-mobility group protein B 1 (HMGB1) and determined whether A disintegrin and metalloproteinase 10 (ADAM10) inhibit this interaction. PATIENTS AND METHODS: The study population included 15 patients with Buerger's disease and 10 healthy donors without a history of giving peripheral blood samples. Cytokine levels were measured using a luminex multiplex assay in plasma. Flow cytometry was used to analyze the subtypes of helper T (Th) cells among peripheral blood mononuclear cells (PBMCs). The effect of ADAM10 on PBMCs was analyzed in vitro. RESULTS: The levels of inflammatory cyto- kines and production of pathogenic Th cells were found to be higher in Korean patients with Buerger's disease. IL-17 treatment induced HMGB1 associated molecules. HMGB1 also induced IL-17 and Th17 associated transcription factors in Buerger's patients. We observed that ADAM10 regulates the interaction between IL-17 and HMGB1 via advanced glycation end products (RAGE)/nuclear factor-kappa B (NF-kappa B) pathway in patients with Buerger's disease. CONCLUSIONS: This study suggests that IL-17 and HMGB1 cytokines contribute to the pathogenesis of Buerger's disease. These results indicate that ADAM10 alleviates inflammation in Buerger's disease via the HMGB1 and RAGE/NF-kappa B signaling pathway and provides insights into the molecular basis of and a potential therapeutic strategy for Buerger's disease.

Automated summary

This study investigated the interaction between IL-17 and HMGB1 in Buerger's disease patients, finding higher levels of inflammatory cytokines and pathogenic Th cells in these patients. It was observed that ADAM10 regulates the interaction between IL-17 and HMGB1 via the RAGE/NF-kappa B pathway in Buerger's disease patients.