Complement C5 regulates the expression of insulin-like growth factor binding proteins in chronic experimental allergic encephalomyelitis

J Neuroimmunol. 2008 Oct 15;203(1):94-103. doi: 10.1016/j.jneuroim.2008.06.040.

Abstract

Complement activation plays a central role in autoimmune demyelination. To explore the possible effects of C5 on post-inflammatory tissue repair, we investigated the transcriptional profile induced by C5 in chronic experimental allergic encephalomyelitis (EAE) using oligonucleotide arrays. We used C5-deficient (C5-d) and C5-sufficient (C5-s) mice to compare the gene expression profile and we found that 390 genes were differentially regulated in C5-s mice as compared to C5-d mice during chronic EAE. Among them, a group of genes belonging to the family of insulin-like growth factor binding proteins (IGFBP) and transforming growth factor (TGF)-beta3 were found most significantly differentially regulated by C5. The dysregulation of these genes suggests that these proteins might be responsible for the gliosis and lack of remyelination seen in C5-d mice with chronic EAE.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Animals, Outbred Strains
  • Blotting, Western
  • Chronic Disease
  • Complement C5 / immunology*
  • Complement C5 / metabolism
  • Connective Tissue Growth Factor / genetics
  • Connective Tissue Growth Factor / metabolism
  • Encephalomyelitis, Autoimmune, Experimental / immunology*
  • Encephalomyelitis, Autoimmune, Experimental / pathology
  • Encephalomyelitis, Autoimmune, Experimental / physiopathology*
  • Female
  • Gene Expression Profiling
  • Gene Expression Regulation / immunology*
  • Gliosis / immunology
  • Gliosis / pathology
  • Immunohistochemistry
  • Insulin-Like Growth Factor Binding Proteins / genetics*
  • Insulin-Like Growth Factor Binding Proteins / metabolism
  • Mice
  • Mice, Congenic
  • Oligonucleotide Array Sequence Analysis
  • Reverse Transcriptase Polymerase Chain Reaction
  • Spinal Cord / immunology
  • Spinal Cord / metabolism
  • Spinal Cord / pathology

Substances

  • Complement C5
  • Insulin-Like Growth Factor Binding Proteins
  • Connective Tissue Growth Factor