In vitro biological activities of glycosylated human interleukin-1a, neoglyco IL-1a, coupled with N-acetylneuraminic acid

• Published in: Glycoconjugate journal 1999-09, Vol.16 (9), p.563-568
• Main Authors: Moriya, Kayoko, Chiba, Taku, Nabeshima, Sachi, Hayashi, Hidetoshi, Onozaki, Kikuo
• Format: Article
• Language: English
• ISSN: 0282-0080; 1573-4986
• DOI: 10.1023/A:1007082207188

In the previous study, N-acetylneuraminic acid (NANA) with C9 spacer was chemically coupled to human recombinant (rh) IL-1a in order to study the effect of glycosylation on its biological activities, and to develop IL-1 with less deleterious effects. In this study we examined a variety of IL-1 activities in vitro, including proliferative effect on T cells, antiproliferative effect on myeloid leukemic cells and melanoma cells, stimulatory effects on IL-6 synthesis by melanoma cells and PGE sub(2) synthesis by fibroblast cells. NANA-introduced IL-1a (NANA-IL-1a) exhibited reduced activities about ten times compared with original IL-1a in all the activities performed in vitro. The competitive binding of super(125)I-IL-1a to mouse T cells and pre-B cells with unlabeled IL-1as suggests the decrease in binding affinities of NANA-IL-1a to both type I and type II IL-1 receptors. Therefore, reduced activities of NANA-IL-1a well correlated with the decrease in its receptor binding affinities.