Synthesis, solution conformation and interleukin-6-related activities of interleukin-6 peptides.
Interleukin-6 (IL-6) is a member of the cytokine superfamily characterised by a wide variety of biological activities on various cell types. IL-6 exerts pleiotropic activities on hematopoiesis in the immune response and it is the main regulator of acute-phase protein synthesis in liver cells. According to structure-function studies, residues of helix A located at the N-terminal part and/or helix D of the C-terminal part of the protein are involved in the induction of acute-phase responses. Two groups of synthetic peptides corresponding to the 18-46 N-terminal and the 168-185 C-terminal regions of the IL-6 were prepared by solid-phase synthesis to identify structural requirements for induction of fibrinogen or complement factor B synthesis. These peptides were characterised by amino acid analysis, analytical reversed-phase high-performance liquid chromatography, fast atom bombardment mass spectrometry, and circular dichroism (CD) spectroscopy. CD results showed that under appropriate conditions both 18-46 and 168-185 related peptides are able to adopt markedly ordered conformation. We demonstrated that even 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 novo synthesis of acute-phase proteins was evaluated by measuring fibrinogen and complement factor B levels in the supernatants of human HepG2 cells. These results showed that residues 21-34 are critical for eliciting fibrinogen synthesis in the presence or absence of IL-6. In contrast, the full-length 168-185 peptide is required for the induction of complement factor B response.
Research Group of Peptide Chemistry, Hungarian Academy of Science, Eötvös Loránd University, Budapest.
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S
Bosze
J
J
Kajtár
R
R
Szabó
A
A
Falus
F
F
Hudecz
D000209:Acute-Phase Proteins / Q000096:biosynthesis / Q000187:drug effects; D000210:Acute-Phase Reaction; D000595:Amino Acid Sequence; D006528:Carcinoma, Hepatocellular; D002942:Circular Dichroism; D011415:Complement Factor B / Q000096:biosynthesis; D005340:Fibrinogen / Q000096:biosynthesis; D006801:Humans; D015850:Interleukin-6 / Q000138:chemical synthesis* / Q000494:pharmacology* / Q000502:physiology; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D010446:Peptide Fragments / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D011487:Protein Conformation; D012996:Solutions; D014407:Tumor Cells, Cultured
D000209:Acute-Phase Proteins; D015850:Interleukin-6; D009842:Oligopeptides; D010446:Peptide Fragments; D012996:Solutions; D005340:Fibrinogen; D011415:Complement Factor B