Regulation of activity of the immune cells by modified peptide fragments of Human IL-2

• Published in: Russian journal of bioorganic chemistry 2012-07, Vol.38 (4), p.360-366
• Main Authors: Onoprienko, L. V., Mikhaleva, I. I., Voytenkov, B. O., Ivanov, V. T.
• Format: Article
• Language: English
• Subjects: Antiinflammatory agents; Biochemistry; Biomedical and Life Sciences; Biomedicine; Bioorganic Chemistry; Blood; Cell activation; Cytotoxicity; Enzymes; Interleukin 2; Interleukin 2 receptors; Ionizing radiation; Life Sciences; Liver; Macrophages; Narcosis; Organic Chemistry; Prednisolone; synthetic peptides; thiopental; Toxins; Transformation
• ISSN: 1068-1620; 1608-330X
• DOI: 10.1134/S1068162012040115

Synthetic peptides corresponding to the 59–72, 60–72, and 61–72 sequence of human interleukin 2 (IL-2) with an acetyl group and methoxygroup on their N- and C-termini, respectively, were shown to exhibit pronounced hepatoprotective properties. These peptides neutralized the toxic effect of such toxins as tetrachloromethane and galactosamine on liver in the in vivo experiments. The action of these peptides resulted in normalization of the duration of thiopental narcosis of the experimental animals and the level of hepatospecific enzymes in their blood. The hepatoprotective activity of the most active peptide (59–72) proved to be similar to that of prednisolone (the well-known anti-inflammatory agent), whereas the bestatine cytotoxic dipeptide had no such hepatoprotective effect. A target of the peptide hepatoprotective effect was shown to be the preliminary activated macrophages. The action of the most active (59–72)-peptide probably induced transformation of the classically activated macrophages into their state close to the alternative activation. We proposed that the hepatoprotective activity of the peptides was associated with their binding to the α-sub-unit of receptor of human IL-2 (IL-2Rα), because one of the binding sites of IL-2 to IL-2Rα was located precisely in this region according to the X-ray studies. Experiments on the influence of the most active (59–72)-peptide on growth of the IL-2 dependent cell line (CTLL) confirmed this proposal. The 3 H-labeled peptide corresponding to the 59–72 sequence of the human IL-2 was shown to bind to the CTLL cells. We assumed that the binding of this peptide was specific and occurred precisely with IL-2Rα and virtually determined the binding constant. Its value (1.41 × 10 −6 M) was comparable with that of the interaction of IL-2 with IL-2Rα (approximately 10 −7 M).