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Nabeshima, Sachi; Chiba, Taku; Takei, Yutaka; Ono, Asako; Moriya, Kayoko; Onozaki, Kikuo

doi:10.1023/a:1006987020372

Cited by 9 publications

(4 citation statements)

References 41 publications

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“…Nabeshima et al . reported that the cytokine glycosylation on receptor binding changed biological activity [32]. These reports indicate that glycosylated cytokines may contribute to disease pathogenesis.…”

Section: Discussionmentioning

confidence: 99%

Fucosyltransferase 1 mediates angiogenesis, cell adhesion and rheumatoid arthritis synovial tissue fibroblast proliferation

et al. 2014

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IntroductionWe previously reported that sialyl Lewisy, synthesized by fucosyltransferases, is involved in angiogenesis. Fucosyltransferase 1 (fut1) is an α(1,2)-fucosyltransferase responsible for synthesis of the H blood group and Lewisy antigens. However, the angiogenic involvement of fut 1 in the pathogenesis of rheumatoid arthritis synovial tissue (RA ST) has not been clearly defined.MethodsAssay of α(1,2)-linked fucosylated proteins in RA was performed by enzyme-linked lectin assay. Fut1 expression was determined in RA ST samples by immunohistological staining. We performed angiogenic Matrigel assays using a co-culture system of human dermal microvascular endothelial cells (HMVECs) and fut1 small interfering RNA (siRNA) transfected RA synovial fibroblasts. To determine if fut1 played a role in leukocyte retention and cell proliferation in the RA synovium, myeloid THP-1 cell adhesion assays and fut1 siRNA transfected RA synovial fibroblast proliferation assays were performed.ResultsTotal α(1,2)-linked fucosylated proteins in RA ST were significantly higher compared to normal (NL) ST. Fut1 expression on RA ST lining cells positively correlated with ST inflammation. HMVECs from a co-culture system with fut1 siRNA transfected RA synovial fibroblasts exhibited decreased endothelial cell tube formation compared to control siRNA transfected RA synovial fibroblasts. Fut1 siRNA also inhibited myeloid THP-1 adhesion to RA synovial fibroblasts and RA synovial fibroblast proliferation.ConclusionsThese data show that α(1,2)-linked fucosylated proteins are upregulated in RA ST compared to NL ST. We also show that fut1 in RA synovial fibroblasts is important in angiogenesis, leukocyte-synovial fibroblast adhesion, and synovial fibroblast proliferation, all key processes in the pathogenesis of RA.

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Section: Discussionmentioning

confidence: 99%

Fucosyltransferase 1 mediates angiogenesis, cell adhesion and rheumatoid arthritis synovial tissue fibroblast proliferation

et al. 2014

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“…This is important for therapeutic application of IL-1. It is of note that Man 2 a-(1-6)-IL-1a, but not GaI-IL-1a, also exhibited a comparable WBC recovering effects as IL-1a [14,17]. Probably GaI-IL-1a is more ef®ciently trapped in the liver than IL-1a, subsequently delivery of IL-1 into bone marrow will be reduced.…”

Section: Discussionmentioning

confidence: 93%

“…Similar to NeuAc-IL-1a, Man 2 a(1-6)-IL-1a possessed the same potency as untreated IL-1a [14]. In contrast, the activity was decreased in GaI-IL-1a [17]. Although the reason is not known, it may be due to the different distribution of these neoIL-1s in the liver.…”

Section: Discussionmentioning

confidence: 94%

“…Furthermore, the tissue distribution of Man 2 a(1-6)-IL-1a differed from that of IL-1a [14]. D-Gal conjugated IL-1a manifested a similar decrease in biological activities in vitro and receptor binding af®nity [15,16], however, the magnitude of its decrease in activities in vivo was less than that in vitro [17]. To study the effect of sialic acid modi®cation on IL-1a activity, we coupled N-acetylneuraminic acid (NeuAc), a major member of sialic acid, to rhIL-1a [18].…”

Section: Introductionmentioning

confidence: 92%

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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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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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Cited by 9 publications

References 41 publications

Fucosyltransferase 1 mediates angiogenesis, cell adhesion and rheumatoid arthritis synovial tissue fibroblast proliferation

Fucosyltransferase 1 mediates angiogenesis, cell adhesion and rheumatoid arthritis synovial tissue fibroblast proliferation

Untitled

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

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