The Experts below are selected from a list of 360 Experts worldwide ranked by ideXlab platform
Kikuo Onozaki - One of the best experts on this subject based on the ideXlab platform.
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in vitro biological activities of glycosylated human Interleukin 1alpha neoglyco il 1alpha coupled with n acetylneuraminic acid
Glycoconjugate Journal, 1999Co-Authors: Kayoko Moriya, Taku Chiba, Sachi Nabeshima, Hidetoshi Hayashi, Kikuo OnozakiAbstract:In the previous study, N-acetylneuraminic acid (NANA) with C9 spacer was chemically coupled to human recombinant (rh) IL-1α 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-1α (NANA-IL-1α) exhibited reduced activities about ten times compared with original IL-1α in all the activities performed in vitro. The competitive binding of 125I-IL-1α to mouse T cells and pre-B cells with unlabeled IL-1αs suggests the decrease in binding affinities of NANA-IL-1α to both type I and type II IL-1 receptors. Therefore, reduced activities of NANA-IL-1α well correlated with the decrease in its receptor binding affinities.
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development of glycosylated human Interleukin 1alpha neoglyco il 1alpha coupled with d galactose monosaccharide biological activities in vivo
Glycoconjugate Journal, 1998Co-Authors: Sachi Nabeshima, Kayoko Moriya, Taku Chiba, Yutaka Takei, Asako Ono, Kikuo OnozakiAbstract:In the previous study, galactose with C9 spacer was chemically coupled to human recombinant (rh) IL-1 alpha 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-1 alpha (Gal-IL-1 alpha) exhibited reduced activities from 10 to 10000 times compared with unmodified IL-1 alpha in all the activities performed in vitro. The competitive binding of 125I-IL-1 alpha to mouse T cells and pre-B cells with unlabeled IL-1 alpha s suggests a decrease in binding affinities of Gal-IL-1 alpha to both type I and type II IL-1 receptors. Therefore, reduced activities of Gal-IL-1 alpha are due, at least partially, to the decrease in their receptor binding affinities.
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development of glycosylated human Interleukin 1alpha neoglyco il 1alpha by coupling with d galactose monosaccharide synthesis and purification
Glycoconjugate Journal, 1998Co-Authors: Taku Chiba, Sachi Nabeshima, Yutaka Takei, Kikuo OnozakiAbstract:In order to develop glycosylated cytokine, recombinant human IL-1 alpha was chemically modified with galactose monosaccharide. Galactose with C9 spacer, 8-(hydrazinocarbonyl)octyl beta-D-galctopyranoside (3), was synthesized by glycosylation of C9 spacer, methyl 9-hydroxynonanoate, with acetobromogalactose, followed by deacetylation and hydrazidation. Total yield of 3 was 43.6% in three steps. Compound 3 was coupled to IL-1 alpha by the acyl azide method. The glycosylated IL-1 was purified by anion-exchange chromatography, and galactose coupled to IL-1 was confirmed by R. communis lectin blotting. Based on the molecular weight, the average number of carbohydrate molecules introduced per molecule of IL-1 alpha was estimated to be 9.1.
Adrienne M Flanagan - One of the best experts on this subject based on the ideXlab platform.
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prostaglandin e2 Interleukin 1alpha and tumor necrosis factor alpha increase human osteoclast formation and bone resorption in vitro
Endocrinology, 1998Co-Authors: C S Lader, Adrienne M FlanaganAbstract:Prostaglandin E2 (PGE2) and the cytokines Interleukin (IL) 1α and tumor necrosis factor (TNF)α increase bone resorption in vivo, but the effect of these agents on osteoclastic bone resorption has never been studied in an in vitro human system. Our recently described human bone marrow culture system, in which osteoclasts are generated (vitronectin and calcitonin receptor-positive cells which resorb bone), was used to study the effects of these agents. Addition of indomethacin to macrophage colony-stimulating factor (M-CSF)-treated cultures nearly abolished osteoclast parameters, indicating that prostaglandins are virtually essential for human osteoclast formation. Additionally, PGE2 dose responsively increased osteoclast numbers and bone resorption. The effects of M-CSF and PGE2 are independent, as demonstrated by unaltered PGE2 concentrations in culture supernatants in spite of the dose-responsive increase in osteoclast parameters in response to M-CSF. The generation of osteoclasts in the presence of PGE2...
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prostaglandin e2 Interleukin 1alpha and tumor necrosis factor alpha increase human osteoclast formation and bone resorption in vitro
Endocrinology, 1998Co-Authors: C S Lader, Adrienne M FlanaganAbstract:Prostaglandin E2 (PGE2) and the cytokines Interleukin (IL) 1alpha and tumor necrosis factor (TNF)alpha increase bone resorption in vivo, but the effect of these agents on osteoclastic bone resorption has never been studied in an in vitro human system. Our recently described human bone marrow culture system, in which osteoclasts are generated (vitronectin and calcitonin receptor-positive cells which resorb bone), was used to study the effects of these agents. Addition of indomethacin to macrophage colony-stimulating factor (M-CSF)-treated cultures nearly abolished osteoclast parameters, indicating that prostaglandins are virtually essential for human osteoclast formation. Additionally, PGE2 dose responsively increased osteoclast numbers and bone resorption. The effects of M-CSF and PGE2 are independent, as demonstrated by unaltered PGE2 concentrations in culture supernatants in spite of the dose-responsive increase in osteoclast parameters in response to M-CSF. The generation of osteoclasts in the presence of PGE2 occurred in favor of CD 14-positive macrophage formation. IL 1alpha and TNFalpha increased osteoclast parameters in a dose-responsive manner. Maximum stimulation yielded culture supernatant levels of PGE2 approximately the same as those concentrations of exogenous PGE2 that dramatically induced osteoclast formation. This osteoclast-inducing effect was inhibited both by indomethacin and by the specific inhibitor of inducible prostaglandin G/H synthase, NS398, and this was reversed by addition of exogenous PGE2. These results demonstrate unequivocally that IL 1alpha and TNFalpha enhance human osteoclast formation and suggest that they mediate their effects through PGE2.
Taku Chiba - One of the best experts on this subject based on the ideXlab platform.
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in vitro biological activities of glycosylated human Interleukin 1alpha neoglyco il 1alpha coupled with n acetylneuraminic acid
Glycoconjugate Journal, 1999Co-Authors: Kayoko Moriya, Taku Chiba, Sachi Nabeshima, Hidetoshi Hayashi, Kikuo OnozakiAbstract:In the previous study, N-acetylneuraminic acid (NANA) with C9 spacer was chemically coupled to human recombinant (rh) IL-1α 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-1α (NANA-IL-1α) exhibited reduced activities about ten times compared with original IL-1α in all the activities performed in vitro. The competitive binding of 125I-IL-1α to mouse T cells and pre-B cells with unlabeled IL-1αs suggests the decrease in binding affinities of NANA-IL-1α to both type I and type II IL-1 receptors. Therefore, reduced activities of NANA-IL-1α well correlated with the decrease in its receptor binding affinities.
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development of glycosylated human Interleukin 1alpha neoglyco il 1alpha coupled with d galactose monosaccharide biological activities in vivo
Glycoconjugate Journal, 1998Co-Authors: Sachi Nabeshima, Kayoko Moriya, Taku Chiba, Yutaka Takei, Asako Ono, Kikuo OnozakiAbstract:In the previous study, galactose with C9 spacer was chemically coupled to human recombinant (rh) IL-1 alpha 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-1 alpha (Gal-IL-1 alpha) exhibited reduced activities from 10 to 10000 times compared with unmodified IL-1 alpha in all the activities performed in vitro. The competitive binding of 125I-IL-1 alpha to mouse T cells and pre-B cells with unlabeled IL-1 alpha s suggests a decrease in binding affinities of Gal-IL-1 alpha to both type I and type II IL-1 receptors. Therefore, reduced activities of Gal-IL-1 alpha are due, at least partially, to the decrease in their receptor binding affinities.
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development of glycosylated human Interleukin 1alpha neoglyco il 1alpha by coupling with d galactose monosaccharide synthesis and purification
Glycoconjugate Journal, 1998Co-Authors: Taku Chiba, Sachi Nabeshima, Yutaka Takei, Kikuo OnozakiAbstract:In order to develop glycosylated cytokine, recombinant human IL-1 alpha was chemically modified with galactose monosaccharide. Galactose with C9 spacer, 8-(hydrazinocarbonyl)octyl beta-D-galctopyranoside (3), was synthesized by glycosylation of C9 spacer, methyl 9-hydroxynonanoate, with acetobromogalactose, followed by deacetylation and hydrazidation. Total yield of 3 was 43.6% in three steps. Compound 3 was coupled to IL-1 alpha by the acyl azide method. The glycosylated IL-1 was purified by anion-exchange chromatography, and galactose coupled to IL-1 was confirmed by R. communis lectin blotting. Based on the molecular weight, the average number of carbohydrate molecules introduced per molecule of IL-1 alpha was estimated to be 9.1.
Sachi Nabeshima - One of the best experts on this subject based on the ideXlab platform.
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in vitro biological activities of glycosylated human Interleukin 1alpha neoglyco il 1alpha coupled with n acetylneuraminic acid
Glycoconjugate Journal, 1999Co-Authors: Kayoko Moriya, Taku Chiba, Sachi Nabeshima, Hidetoshi Hayashi, Kikuo OnozakiAbstract:In the previous study, N-acetylneuraminic acid (NANA) with C9 spacer was chemically coupled to human recombinant (rh) IL-1α 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-1α (NANA-IL-1α) exhibited reduced activities about ten times compared with original IL-1α in all the activities performed in vitro. The competitive binding of 125I-IL-1α to mouse T cells and pre-B cells with unlabeled IL-1αs suggests the decrease in binding affinities of NANA-IL-1α to both type I and type II IL-1 receptors. Therefore, reduced activities of NANA-IL-1α well correlated with the decrease in its receptor binding affinities.
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development of glycosylated human Interleukin 1alpha neoglyco il 1alpha coupled with d galactose monosaccharide biological activities in vivo
Glycoconjugate Journal, 1998Co-Authors: Sachi Nabeshima, Kayoko Moriya, Taku Chiba, Yutaka Takei, Asako Ono, Kikuo OnozakiAbstract:In the previous study, galactose with C9 spacer was chemically coupled to human recombinant (rh) IL-1 alpha 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-1 alpha (Gal-IL-1 alpha) exhibited reduced activities from 10 to 10000 times compared with unmodified IL-1 alpha in all the activities performed in vitro. The competitive binding of 125I-IL-1 alpha to mouse T cells and pre-B cells with unlabeled IL-1 alpha s suggests a decrease in binding affinities of Gal-IL-1 alpha to both type I and type II IL-1 receptors. Therefore, reduced activities of Gal-IL-1 alpha are due, at least partially, to the decrease in their receptor binding affinities.
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development of glycosylated human Interleukin 1alpha neoglyco il 1alpha by coupling with d galactose monosaccharide synthesis and purification
Glycoconjugate Journal, 1998Co-Authors: Taku Chiba, Sachi Nabeshima, Yutaka Takei, Kikuo OnozakiAbstract:In order to develop glycosylated cytokine, recombinant human IL-1 alpha was chemically modified with galactose monosaccharide. Galactose with C9 spacer, 8-(hydrazinocarbonyl)octyl beta-D-galctopyranoside (3), was synthesized by glycosylation of C9 spacer, methyl 9-hydroxynonanoate, with acetobromogalactose, followed by deacetylation and hydrazidation. Total yield of 3 was 43.6% in three steps. Compound 3 was coupled to IL-1 alpha by the acyl azide method. The glycosylated IL-1 was purified by anion-exchange chromatography, and galactose coupled to IL-1 was confirmed by R. communis lectin blotting. Based on the molecular weight, the average number of carbohydrate molecules introduced per molecule of IL-1 alpha was estimated to be 9.1.
C S Lader - One of the best experts on this subject based on the ideXlab platform.
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prostaglandin e2 Interleukin 1alpha and tumor necrosis factor alpha increase human osteoclast formation and bone resorption in vitro
Endocrinology, 1998Co-Authors: C S Lader, Adrienne M FlanaganAbstract:Prostaglandin E2 (PGE2) and the cytokines Interleukin (IL) 1α and tumor necrosis factor (TNF)α increase bone resorption in vivo, but the effect of these agents on osteoclastic bone resorption has never been studied in an in vitro human system. Our recently described human bone marrow culture system, in which osteoclasts are generated (vitronectin and calcitonin receptor-positive cells which resorb bone), was used to study the effects of these agents. Addition of indomethacin to macrophage colony-stimulating factor (M-CSF)-treated cultures nearly abolished osteoclast parameters, indicating that prostaglandins are virtually essential for human osteoclast formation. Additionally, PGE2 dose responsively increased osteoclast numbers and bone resorption. The effects of M-CSF and PGE2 are independent, as demonstrated by unaltered PGE2 concentrations in culture supernatants in spite of the dose-responsive increase in osteoclast parameters in response to M-CSF. The generation of osteoclasts in the presence of PGE2...
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prostaglandin e2 Interleukin 1alpha and tumor necrosis factor alpha increase human osteoclast formation and bone resorption in vitro
Endocrinology, 1998Co-Authors: C S Lader, Adrienne M FlanaganAbstract:Prostaglandin E2 (PGE2) and the cytokines Interleukin (IL) 1alpha and tumor necrosis factor (TNF)alpha increase bone resorption in vivo, but the effect of these agents on osteoclastic bone resorption has never been studied in an in vitro human system. Our recently described human bone marrow culture system, in which osteoclasts are generated (vitronectin and calcitonin receptor-positive cells which resorb bone), was used to study the effects of these agents. Addition of indomethacin to macrophage colony-stimulating factor (M-CSF)-treated cultures nearly abolished osteoclast parameters, indicating that prostaglandins are virtually essential for human osteoclast formation. Additionally, PGE2 dose responsively increased osteoclast numbers and bone resorption. The effects of M-CSF and PGE2 are independent, as demonstrated by unaltered PGE2 concentrations in culture supernatants in spite of the dose-responsive increase in osteoclast parameters in response to M-CSF. The generation of osteoclasts in the presence of PGE2 occurred in favor of CD 14-positive macrophage formation. IL 1alpha and TNFalpha increased osteoclast parameters in a dose-responsive manner. Maximum stimulation yielded culture supernatant levels of PGE2 approximately the same as those concentrations of exogenous PGE2 that dramatically induced osteoclast formation. This osteoclast-inducing effect was inhibited both by indomethacin and by the specific inhibitor of inducible prostaglandin G/H synthase, NS398, and this was reversed by addition of exogenous PGE2. These results demonstrate unequivocally that IL 1alpha and TNFalpha enhance human osteoclast formation and suggest that they mediate their effects through PGE2.