RESUMEN
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 cytokines 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-kB) 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-κB signaling pathway and provides insights into the molecular basis of and a potential therapeutic strategy for Buerger's disease.
Asunto(s)
Citocinas/inmunología , Proteína HMGB1/inmunología , Tromboangitis Obliterante/inmunología , Proteína ADAM10/inmunología , Adulto , Secretasas de la Proteína Precursora del Amiloide/inmunología , Células Cultivadas , Citocinas/sangre , Citocinas/genética , Femenino , Proteína HMGB1/sangre , Proteína HMGB1/genética , Humanos , Leucocitos Mononucleares/inmunología , Masculino , Proteínas de la Membrana/inmunología , Persona de Mediana Edad , FN-kappa B/inmunología , Miembro 3 del Grupo F de la Subfamilia 1 de Receptores Nucleares/genética , Receptor para Productos Finales de Glicación Avanzada/genética , Tromboangitis Obliterante/sangre , Tromboangitis Obliterante/genéticaRESUMEN
A simple process for fast fabrication of thin films with biomimetic morphological structures from a group of linear homopolymers is developed. Natural evaporation of tetrahydrofuran, chloroform, and hexane-dichloromethane solutions of poly(phenylacetylene)s that contain amino acid and ethylene glycol moieties under ambient conditions instantly produces three-dimensional porous films with structural patterns reminiscent of honeycombs and radiolarian shells. Morphological analysis by optical and electronic microscopy suggests that vesicles of the amphiphilic polymers serve as building blocks in the self-organization to the biomimetic structures.