RESUMO
BACKGROUND: ß2-glycoprotein I (ß2GPI)-dependent antiphospholipid antibodies (aPLs) are considered to play a pivotal pathogenic role in antiphospholipid syndrome (APS) by inducing the expression of tissue factor, inflammatory cytokines, and chemokines, most of which are dependent upon the NF-κB pathway. Therefore, the NF-κB is regarded as a promising target for the development of a novel therapeutic strategy. However, progress has been limited owing to the fact that there are no widely-used in vivo models, or highly specific inhibitors. OBJECTIVE: This study aimed to test the effects of an NF-κB-specific inhibitor, DHMEQ, in preventing thrombus formation using an original mouse model of APS. MATERIALS AND METHODS: Specificity of a monoclonal aPL WB-6 was examined by ELISA. WB-6 was injected into normal BALB/c mice with or without DHMEQ treatment. A pulse laser was radiated to a cutaneous vein in the window of a dorsal skinfold chamber attached to the mouse and thrombus formation was observed and recorded under a microscope. RESULTS: WB-6 bound preferentially to the caldiolipin (CL)-ß2GPI complex rather than to CL alone, or ß2GPI alone. WB-6, but not isotype-matched control antibody, induced a prothrombotic state in the mice by inducing tissue factor expression upon circulating monocytes, resulting in thrombus formation at the site of laser-induced endothelial injury. This diathesis was almost completely ameliorated by DHMEQ treatment. CONCLUSIONS: Inhibition of the NF-κB pathway is a promising strategy for the development of a novel treatment for APS.
