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Abstract
Background Breakdown of the blood-brain barrier (BBB) integrity is required for the development of psychiatric manifestations in SLE (NPSLE), especially in lupus psychosis for the direct attack by autoantibodies against neurons. The aim of this study is to investigate the direct effect of anti-Smith antibody (anti-Sm) on BBB integrity via matrix metalloproteinase (MMP)-2 and evaluate the effect of captopril, a MMP-2 inhibitor on preventing BBB breach.
Methods Human umbilical vein endothelial cells (HUVEC) were stimulated with monoclonal anti-Sm or anti-RNP antibody (anti-RNP). BBB integrity was evaluated with claudin-5 expression, the tight junction composing protein by q-PCR, and western blot. MMP-2 activity was measured by gelatin zymography.
Results Antibody stimulation with anti-Sm or anti-RNP did not affect the expression of MMP-2 and claudin-5 at mRNA level. However, Claudin-5 protein expression was significantly reduced by anti-Sm stimulation compared to isotype control (p=0.004), but not by anti-RNP (p=0.496) (figure 1A). Active MMP-2 in culture supernatant was significantly increased after anti-Sm stimulation (p=0.015), but not by anti-RNP (p=0.688) (figure 1B). Addition of captopril restored claudin-5 mRNA expression that was reduced by anti-Sm stimulation (p=0.031) (figure 1C).
Conclusions Anti-Sm reduced claudin-5 expression in HUVEC through up-regulation of active MMP-2 expression. Our results suggest that Captopril can be protective for BBB breaches mediated by anti-Sm in patients with NPSLE.
Claudin-5 and active MMP-2
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