S. Bosze et al., SYNTHESIS, SOLUTION CONFORMATION AND INTERLEUKIN-6-RELATED ACTIVITIESOF INTERLEUKIN-6 PEPTIDES, The journal of peptide research, 52(3), 1998, pp. 216-228
Interleukin-6 (IL-6) is a member of the cytokine superfamily character
ised by a wide variety of biological activities on various cell types.
IL-6 exerts pleiotropic activities on hematopoiesis in the immune res
ponse and it is the main regulator of acute-phase protein synthesis in
liver cells. According to structure-function studies, residues of hel
ix A located at the N-terminal part and/or helix D of the C-terminal p
art of the protein are involved in the induction of acute-phase respon
ses. Two groups of synthetic peptides corresponding to the 18-46 N-ter
minal and the 168-185 C-terminal regions of the IL-6 were prepared by
solid-phase synthesis to identify structural requirements for inductio
n of fibrinogen or complement factor B synthesis. These peptides were
characterised by amino acid analysis, analytical reversed-phase high-p
erformance liquid chromatography, fast atom bombardment mass spectrome
try, and circular dichroism (CD) spectroscopy. CD results showed that
under appropriate conditions both 18-46 and 168-185 related peptides a
re able to adopt markedly ordered conformation. We demonstrated that e
ven octapeptides from the N-terminal part and truncated derivatives of
the C-terminal region preserved some tendency to display the CD curve
of periodic conformation. The ability of the peptides to induce de no
vo synthesis of acute-phase proteins was evaluated by measuring fibrin
ogen and complement factor B levels in the supernatants of human HepG2
cells. These results showed that residues 21-34 are critical for elic
iting fibrinogen synthesis in the presence or absence of IL-6. In cont
rast, the full-length 168-185 peptide is required for the induction of
complement factor B response.