TY - JOUR
T1 - Development of glycosylated human interleukin-1α, neoglyco IL-1α, by coupling with D-galactose monosaccharide
T2 - Biological activities in vitro
AU - Nabeshima, Sachi
AU - Chiba, Taku
AU - Takei, Yutaka
AU - Watanabe, Shiro
AU - Okuyama, Harumi
AU - Onozaki, Kikuo
N1 - Funding Information:
We thank Dr H. Hayashi for valuable suggestions and Mr M. Hayashi for technical assistance. This work was supported in part by grants from the Ministry of Education, Science and Culture of Japan and The Research Foundation for Parmaceutical Science.
PY - 1998
Y1 - 1998
N2 - In the previous study, galactose with C9 spacer was chemically coupled to human recombinant (rh) IL-1α in order to study the effect of glycosylation on its 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 Galactose-introduced IL-1α (Gal-IL-1α) exhibited reduced activities from 10 to 10000 times compared with unmodified IL-1α in all the activities performed in vitro. The competitive binding of 125HL-1α to mouse T cells and pre-B cells with unlabeled IL-1α s suggests a decrease in binding affinities of Gal-IL-1α to both type I and type II IL-1 receptors. Therefore, reduced activities of Gal-IL-1α are due, at least partially, to the decrease in their receptor binding affinities.
AB - In the previous study, galactose with C9 spacer was chemically coupled to human recombinant (rh) IL-1α in order to study the effect of glycosylation on its 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 Galactose-introduced IL-1α (Gal-IL-1α) exhibited reduced activities from 10 to 10000 times compared with unmodified IL-1α in all the activities performed in vitro. The competitive binding of 125HL-1α to mouse T cells and pre-B cells with unlabeled IL-1α s suggests a decrease in binding affinities of Gal-IL-1α to both type I and type II IL-1 receptors. Therefore, reduced activities of Gal-IL-1α are due, at least partially, to the decrease in their receptor binding affinities.
KW - Cytokine
KW - Interleukin 1
KW - Neoglycoprotein
UR - http://www.scopus.com/inward/record.url?scp=0031884599&partnerID=8YFLogxK
U2 - 10.1023/A:1006943500806
DO - 10.1023/A:1006943500806
M3 - 学術論文
C2 - 9530958
AN - SCOPUS:0031884599
SN - 0282-0080
VL - 15
SP - 69
EP - 74
JO - Glycoconjugate Journal
JF - Glycoconjugate Journal
IS - 1
ER -