Conclusion
Together, these findings suggest a potential antiatherosclerotic capacity of laquinimod. Further research will elucidate the underlying mechanisms.
Methods
The effects of laquinimod on the gene expression of IL-6, MCP-1, VCAM-1, E-selectin, and KLF2 were measured by real-time PCR. ELISA assay was used to determine protein secretion and expression. Phosphorylation of ERK5 and the protein level of KLF2 were measured by Western blot analysis. The attachment of monocytes to endothelial cells was assayed by calcein-AM staining and fluorescent microscopy.
Results
Our findings demonstrate that laquinimod reduced the expression of key inflammatory cytokines and chemokines, including IL-6, MCP-1, and HMGB1. We further demonstrate that laquinimod significantly reduced the attachment of monocytes to endothelial cells, which is mediated through reduced expression of the cellular adhesion molecules VCAM-1 and E-selectin. Here, we found that laquinimod could significantly increase the expression of KLF2 through activation of ERK5 signaling. The results of our KLF2 knockdown experiment confirm that the effects of laquinimod observed in vitro are dependent on KLF2 expression.