RESUMO
Inhibitors of apoptosis proteins (IAPs) block cell death in response to diverse stimuli. The mitochondrial protein, second mitochondria-derived activator of caspase (Smac), negatively regulates IAP inhibition of caspase activity. We investigated the proapoptotic activity of a synthetic Smac (Smac 066) on fibroblast-like synoviocytes (FLS) derived from patients with active rheumatoid arthritis (RA). We found that Smac 066 induced significant apoptosis in all RA-FLS samples. Furthermore, IAPs, which are upregulated in RA-FLS, were downregulated by Smac 066. This suggested that IAPs upregulation was responsible for RA-FLS sensitivity to Smac 066. Next, we analysed caspase activation and found that Smac 066 was associated with caspase 8 and caspase 3 activities. We then investigated the mechanism underlying Smac 066 downregulation of IAPs in RA-FLS with an apoptotic pathway array. Interestingly, Smac 066 significantly upregulated IGFBP-5, a protein involved in differentiation, apoptosis, and osteoblastic activation. Smac 066 may represent a new therapeutic approach to RA treatment.
Assuntos
Apoptose/efeitos dos fármacos , Artrite Reumatoide/patologia , Materiais Biomiméticos/farmacologia , Fibroblastos/efeitos dos fármacos , Peptídeos e Proteínas de Sinalização Intracelular/farmacologia , Proteínas Mitocondriais/farmacologia , Líquido Sinovial/efeitos dos fármacos , Antirreumáticos/farmacologia , Apoptose/fisiologia , Proteínas Reguladoras de Apoptose , Células Cultivadas , Fibroblastos/patologia , Humanos , Líquido Sinovial/citologiaRESUMO
126 enamellers and 64 decorators from 5 factories underwent dermatological and allergological examination using occupational test series in order to evaluate the prevalence of dermatitis and contact sensitization, and to identify the most important sensitizing substances. 48 workers (corresponding to 25.26% of the study population) were sensitized, with a total of 55 positive patch tests. Dermatitis was present in 22 workers, whereas 44 subjects claimed to have had skin lesions in the past. We found 17 positivities to specific substances: 7 to red iron oxide; 2 to antimony trioxide, manganese dioxide and maleic anhydride; and 1 to red copper oxide, cadmium chloride, vanadium pentoxide and sodium tripolyphosphate.