GSK-3 and ROS (reactive oxygen species) inhibition modulate Vimentin expression

Abstract: When exposed to pathogenic stress, cellular processes and survival are dependent on cytoskeletal proteins for structure and organisation of the cell to adapt and maintain homeostasis during inflammation. Vimentin is type III cytoskeletal protein, with an extensive cytoplasmic meshwork, across the cell and regulate the cell structure and cellular space and expressed strongly under tumorigenic events. GSK-3, a regulatory component of inflammation expressed in abundance of cell together with reactive oxygen species (ROS), a group of key complex signalling molecules that are oxygen metabolites which are partially reduced, with robust oxidising abilities, are believed to influence inflammasome formation and specifically vimentin expression upon inflammation. This project investigated the potential modulation vimentin mRNA expression utilising the two signal NLRP3 inflammasome activation theory, by inhibiting GSK-3 and ROS in signal I and or signal II in LPS and nigericin stimulated THP-1 cells, compared to non-inhibited LPS and nigericin THP-1 cells. Inhibition of GSK-3 in signal II downregulated vimentin expression, reflecting repressed phosphorylation of GSK-3 hence also the components required for vimentin; whilst upregulation of vimentin in signal I, reflects possible alternative pathways phosphorylating vimentin components. Overall upregulation of vimentin upon inhibiting ROS in both signal I and II, further proved that inflammasome activation is independent of ROS in the priming step. More research is required integrating vimentin activity and either GSK-3 or ROS, as the potential of these prominent inflammatory markers and their major regulatory presence across an abundance of cell may contribute to the future of drug development for inflammatory diseases.