In vitro biological activities of glycosylated human interleukin-1alpha, neoglyco IL-1alpha, coupled with N-acetylneuraminic acid.
In the previous study, N-acetylneuraminic acid (NANA) with C9 spacer was chemically coupled to human recombinant (rh) IL-1alpha 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 PGE2 synthesis by fibroblast cells. NANA-introduced IL-1alpha (NANA-IL-1alpha) exhibited reduced activities about ten times compared with original IL-1alpha in all the activities performed in vitro. The competitive binding of 125I-IL-1alpha to mouse T cells and pre-B cells with unlabeled IL-1alphas suggests the decrease in binding affinities of NANA-IL-1alpha to both type I and type II IL-1 receptors. Therefore, reduced activities of NANA-IL-1alpha well correlated with the decrease in its receptor binding affinities.
Moriya
K
K
Department of Hygeinic Chemistry, Faculty of Pharmaceutical Sciences, Nagoya City University, Mizuho, Japan.
Chiba
T
T
Nabeshima
S
S
Hayashi
H
H
Onozaki
K
K
D000818:Animals; D001402:B-Lymphocytes / Q000378:metabolism; D002455:Cell Division; D002478:Cells, Cultured; D015232:Dinoprostone / Q000096:biosynthesis; D006023:Glycoproteins / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D006031:Glycosylation; D006801:Humans; D007375:Interleukin-1 / Q000737:chemistry*; D015850:Interleukin-6 / Q000096:biosynthesis; D051379:Mice; D019158:N-Acetylneuraminic Acid / Q000737:chemistry*; D011485:Protein Binding; D011994:Recombinant Proteins / Q000737:chemistry; D013601:T-Lymphocytes / Q000378:metabolism; D014407:Tumor Cells, Cultured
D006023:Glycoproteins; D007375:Interleukin-1; D015850:Interleukin-6; D011994:Recombinant Proteins; D019158:N-Acetylneuraminic Acid; D015232:Dinoprostone