Studies on the contribution of c-fos/AP-1 to arthritic joint destruction.

AUTOR(ES)

Shiozawa, S

RESUMO

Features characteristic to rheumatoid joint destruction, including synovial overgrowth and bone resorption, are experimentally produced by augmenting c-fos gene expression. We tested here if arthritic joint destruction was inhibited upon inactivation of the c-fos/AP-1 signal by administering short double-stranded AP-1 DNA oligonucleotides into mice with collagen-induced arthritis to compete for the binding of AP-1 in vivo at the promoter binding site. Arthritic joint destruction was inhibited in a sequence-specific and dose-dependent manner by oligonucleotides containing the AP-1 sequence. The oligonucleotides inhibited gene expression at the transcriptional level. Nucleotide sequences besides AP-1 also appeared to be important structurally for binding of AP-1 onto DNA and for the stability of oligonucleotides against nucleases. Immunohistochemical chase experiment administering biotinylated oligonucleotides into arthritic mice showed that AP-1 oligonucleotides reached the inflamed joint. Thus, activation of c-fos/AP-1 appears essentially important in arthritic joint destruction.

Documentos Relacionados

• Effect of combined heat and radiation on microbial destruction.
• The C-Terminal Domain of c-fos Is Required for Activation of an AP-1 Site Specific for jun-fos Heterodimers
• Insulin-secreting non-islet cells are resistant to autoimmune destruction.
• Gratuitous overexpression of genes in Escherichia coli leads to growth inhibition and ribosome destruction.
• Epstein-Barr virus BZLF1 trans-activator specifically binds to a consensus AP-1 site and is related to c-fos.