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Chiba, Taku; Nabeshima, Sachi; Takei, Yutaka; Onozaki, Kikuo

doi:10.1023/a:1006991416735

Cited by 8 publications

(2 citation statements)

References 12 publications

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“…In vivo system is more complex than that in vitro and the potency of IL-1 activity may not be determined solely by its af®nity to IL-1RI. In accordance with our results in the present study, Man 2 a(1,6)-IL-1a also exhibits comparable activities as IL-1a to decrease serum glucose level and to improve the recovery of WBC in 5-FU treated mice, although its binding af®nity to IL-1RI was markedly decreased [12,13]. There are many factors affecting IL-1 binding to IL-1RI and the process for exerting its function.…”

Section: Discussionsupporting

confidence: 90%

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Sasayama

Moriya

Chiba

et al. 2000

Glycoconjugate Journal

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In order to study the effect of glycosylation on its biological activities and to develop IL-1 with less deleterious effects, N-acetylneuraminic acid (NeuAc) with C9 spacer was chemically coupled to human recombinant IL-1alpha. NeuAc-coupled IL-1alpha (NeuAc-IL-1alpha) exhibited reduced activities in vitro and receptor-binding affinities by about ten times compared to IL-1alpha. In this study, we examined a variety of IL-1 activities in vivo. NeuAc-IL-1alpha exhibited a marked reduction in the activity to up-regulate serum IL-6, moderate reduction in the activities to up-regulate serum amyloid A and NOx. However, it exhibited comparable activities as IL-1alpha to down-regulate serum glucose and to improve the recovery of peripheral white blood cells from myelosuppression in 5-fluorouracil-treated mice. In addition, tissue level of NeuAc-IL-1alpha was high compared to IL-1alpha. These results indicate that coupling with NeuAc enabled us to develop neo-IL-1 with selective activities in vivo and enhanced tissue level.

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Section: Discussionsupporting

confidence: 90%

“…D-Mana(1-6)Man[Man 2 a(1-6)] conjugated rh IL-1a exhibited a decrease in biological activities in vitro and receptor binding af®nity compared to IL-1a [12]. However, Man 2 a(1-6)-IL-1a exhibited selective activities in vivo [13]. Furthermore, the tissue distribution of Man 2 a(1-6)-IL-1a differed from that of IL-1a [14].…”

Section: Introductionmentioning

confidence: 99%

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Sasayama

Moriya

Chiba

et al. 2000

Glycoconjugate Journal

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Synthesis of glycosylated human tumor necrosis factor α coupled with N-acetylneuraminic acid

Hayashi

Chiba

Hayashi

et al. 2006

Cancer Immunol Immunother

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In order to study the effect of glycosylation on its biological activities, and to develop TNFalpha with less deleterious effects, recombinant human TNFalpha was chemically coupled with N-acetylneuraminic acid (NeuAc). NeuAc with C9 spacer was coupled to TNFalpha by acyl azide method. Two glycosylated TNFalphas, designated L NeuAc-TNFalpha and H NeuAc-TNFalpha, were purified by anion-exchange chromatography. NeuAc coupling to TNFalpha was confirmed by lectin blotting. Average number of carbohydrate molecules introduced per molecule of L NeuAc-TNFalpha and H NeuAc-TNFalpha were estimated to be 1.0 and 1.5, respectively. We examined a variety of TNFalpha activities in vitro, including antiproliferative or cytotoxic activities to tumor cells, proliferative effect on fibroblast cells, stimulatory effects on IL-6 production by melanoma cells and NF-kappaB activation in hepatoma cells. L NeuAc-TNFalpha and H NeuAc-TNFalpha exhibited reduced activities about 1/3 and 1/10 as compared to native TNFalpha in all the activities performed in vitro.

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