The Pro-Inflammatory Role of Vimentin in the Colon

Inflammatory Bowel Disease (IBD) is most frequently manifested by ulceration and chronic inflammation of the gastrointestinal tract and is associated with increased risk of colorectal cancer. IBD is believed to be caused by an abnormal immune response to commensal bacteria, as well as environmental factors and genetic predisposition. Recent treatments for IBD include anti-inflammatory drugs, which may increase the risk of secondary infections and cancer, thereby increasing the need for preventative care and improved treatment modalities.

Two distinct studies of human tissue of gene expression during the course of IBD have shown increased vimentin, expression especially in ulcerative colitis. In addition, interaction between vimentin and nucleotide binding oligomerization domain-containing protein 2 (NOD-2) has been found. Despite these findings, vimentin’s function and its role in IBD remain elusive.

We now suggest a new role for the vimentin protein in intestinal homeostasis. Using E. coli and dextran sodium sulfate (DSS)-induced colitis mouse models, we have found that Vim -/- mice show significant resistance to the development of acute and chronic colitis, while under steady state conditions Vim -/- mice have a remarkable normal phenotype and very subtle abnormalities. Moreover, in a model of colitis-associated tumors induced by azoxymethane (AOM) and DSS, vimentin -/- mice developed significantly less tumors than wild-type mice under the same conditions. Our results suggest that vimentin suppress the production of reactive oxygen species (ROS) and autophagy. In addition, vimentin can induce production of pro-inflammatory cytokines such as IL-1β and IL-6. Thus, we concluded that vimentin support chronic inflammation of the colon and promote tumorogenesis.