C-terminal peptides of interleukin-6 modulate the expression of junB protooncogene and the production of fibrinogen by HepG2 cells

Interleukin-6 (IL-6) is a 185 amino acid residue helical cytokine with vari ous biological activities (e. g. B cell development, acute phase reaction). We have investigated the role of the 168-185 C-terminal region of IL-6 in the induction of fibrinogen synthesis and expression of junB mRNA using syn thetic peptides corresponding to this region. Circular dichroism spectrosco py data suggest that even truncated peptides have a strong tendency to adop t an ordered conformation. Peptides were tested alone or in combination wit h recombinant hIL-6 on an IL-6 responsive human hepatoma HepG2 cell line. T he expression of the protooncogene junB monitored by competitive RT-PCR rep resents an early, while the fibrinogen production detected by sandwich ELIS A a late, marker of IL-6 initiated events. We found that peptides - dependi ng on their structure - modulate spontaneous as well as IL-6 induced fibrin ogen production and/or mRNA expression of junB by exhibiting inhibition (in the presence of IL-6) or stimulation (in the absence of IL-6).