Complement C5 regulates insulin-like growth factors binding proteins in chronic Experimental Autoimmune Encephalomyelitis (EAE) (53.8)

Abstract

Abstract Complement activation plays a central role in autoimmune demyelination. We have analyzed the role of complement C5 in EAE using C5-deficient (C5-d) and C5-sufficient (C5-s) mice and found that the absence of C5 resulted in fiber loss and extensive scarring. In this study, we investigated thetranscriptional profile induced by C5 in chronic EAE using oligonucleotide array.During chronic EAE (day 90, post-immunization), we found that 462 genes were differentially regulated in C5-s when compared with C5-d mice. The majority of these genes were related to cell growth and signal transduction; agroup of genes belonging to the insulin-like growth factors binding proteins family was also significantly regulated by C5. This category include insulin like growth factors (IGFBP) 3, 4 and 6, connective tissue growth factor (CTGF), WNT1 inducible signaling pathway protein 2, cysteine rich protein 61 and endothelial cell specific molecule-1. Using Real-time PCR we confirmed the down-regulation of these genes in C5-d mice in chronic EAE. When IGFBP3 and CTGF levels in chronic EAE were compared with those in control mice (day 0, post-immunization), significantly lower levels of mRNA expression were found only in C5-d mice. The down-regulation of genes belonging to the insulin-like growth factor binding family suggests that they might be responsible for the axonal loss and gliosis seen in C5-d during chronic EAE.