Vimentin neutralizing antibody ameliorate inflammatory bowel disease by inhibiting fibrosis and inflammatory cell...

Inflammatory bowel disease (IBD) is characterized by chronic inflammation intertwined with fibrosis and increased necroptosis. Vimentin, an intermediate filament protein closely associated with fibrosis and several inflammatory pathways, is elevated in IBD tissues. We conducted experiments to determine the effect of neutralization of extracellular vimentin with an anti-vimentin antibody (Ab) on the pathogenesis of IBD.

IBD was mimicked in a 7-week C57BL6 mice by mixing 3% dextran sodium sulfate (DSS) in autoclaved drinking water for five days. Anti-vimentin Ab was intraperitoneally injected with a concentration of 3 milligrams per kilogram repeatedly in a three-day interval simultaneously with DSS administration.

In dextran sodium sulfate (DSS)-induced colitis mice, the anti-vimentin Ab decreased the levels of total and cell-surface vimentin in colon tissues compared to control-treated mice. In DSS-induced colitis mice, treatment with the anti-vimentin Ab improved body weight loss and colon shortening, thereby reducing the severity of DSS-induced colitis. In addition, the anti-vimentin Ab reduced the number of cells expressing fibrosis markers, inflammatory cytokines, and necroptotic markers in colon tissues of DSS-induced colitis mice. In CCD-18CO human colon epithelial cells, the increases in the levels of fibrosis markers caused by TGFβ were enhanced by vimentin protein stimulation and the anti-vimentin Ab reduced the levels of fibrosis-related factors.

This is the first report of the therapeutic effect of an anti-vimentin Ab on the pathogenic mechanisms of IBD. Further studies are needed to confirm its therapeutic potential in clinical settings.