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Renkonen, Risto; Mattila, Pirkko; Majuri, Marja‐Leena; Räbinä, Jarkko; Toppila, Sanna; Renkonen, Jutta; Hirvas, Laura; Niittymäki, Jaana; Turunen, Juha Pekka; Renkonen, Ossi; Paavonen, Timo

doi:10.1023/a:1018536509950

Cited by 43 publications

(12 citation statements)

References 87 publications

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“…7A, IL-4-induced STAT6 was able to form a complex on the 3Ј-half-site (lane 15), while IFN␥ stimulated primarily the formation of the high mobility complex ␥RF-2 (lane 14). Interestingly, when the 5Ј-half-site was used as probe (lanes [17][18][19][20], neither IFN␥ nor IL-4 induced any detectable complex formation. These results indicate that while the 3Ј-half-site of the ␥RE motif is sufficient for STAT6 binding and for ␥RF-2, formation of ␥RF-1 requires both the 3Ј-and 5Ј-half-sites.…”

Section: Fig 4 Effects Of Ifn␥ and Il-4 On Transcription From The Mmentioning

confidence: 99%

“…At least a portion of the anti-inflammatory function of IL-4 is targeted to mononuclear phagocytes where expression of inducible genes encoding cytokines (e.g. TNF␣, IL-1␣, IL-1␤, various chemokines) (6 -16) and cell surface molecules (FcR␥ and ICAM-1) (17,18) is suppressed, while expression of other anti-inflammatory products such as the IL-1 receptor antagonist is amplified (9 -11, 19, 20).…”

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confidence: 99%

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STAT6 Is Required for the Anti-inflammatory Activity of Interleukin-4 in Mouse Peritoneal Macrophages

Ohmori

Hamilton

1998

Journal of Biological Chemistry

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Interleukin-4 (IL-4 Regulation of inflammatory and immune responses involves intercellular communication through a network of secreted cytokines (1). Cytokines derived from T helper (Th)1 1 cells (prototypically IFN␥) promote the development of cellular immunity, while Th2-derived cytokines such as IL-4 promote humoral immunity and antagonize Th1-dependent activities (2-5). At least a portion of the anti-inflammatory function of IL-4 is targeted to mononuclear phagocytes where expression of inducible genes encoding cytokines (e.g. TNF␣, IL-1␣, IL-1␤, various chemokines) (6 -16) and cell surface molecules (FcR␥ and ICAM-1) (17, 18) is suppressed, while expression of other anti-inflammatory products such as the IL-1 receptor antagonist is amplified (9 -11, 19, 20).The molecular mechanisms mediating cytokine-induced gene transcription have been extensively characterized in recent studies on the Janus kinase (JAK) family of protein tyrosine kinases and signal transducers and activators of transcription (STATs) (21-25). IFN␥ has been shown to induce phosphorylation of STAT1, which, in homodimeric form, binds to the IFN␥ activation sequence (GAS) found in many IFN␥-inducible genes (26 -29). In similar fashion, IL-4 stimulates tyrosine phosphorylation of STAT6 (30 -32), which can bind to GAS motifs as well as IL-4-responsive STAT binding elements (SBEs) found in IL-4-inducible genes (20,(33)(34)(35)(36)(37). Interestingly, STAT6 exhibits transactivating function only in the context of a subset of SBE sequence motifs (20,34,(37)(38)(39)(40).IL-4 and IFN␥ exhibit antagonistic effects on macrophage gene expression (14 -18). We have previously observed that IFN␥-mediated induction and IL-4-mediated suppression utilize the same regulatory sequences (the ISRE in the IP-10 gene and the GAS motif in the IRF-1 gene) (16, 40). Furthermore, IL-4 does not inhibit the activation of STAT1 by IFN␥ and IL-4-induced STAT6 is able to bind the IFN␥-responsive site without transactivation (40). Recent studies have shown that STAT1-dependent transcription requires transcriptional coactivators p300 and CREB-binding protein (CBP), which may be present in limiting amounts (41,42). On the basis of these lines of evidence, we postulated that the inhibitory effect of IL-4 may result, at least in part, from the direct action of IL-4-induced STAT6 on IFN␥-induced STAT1-dependent transcription. The present study was undertaken to determine if IL-4-induced STAT6 is required for the suppressive action of IL-4 on IFN␥-induced gene transcription and to extend our analysis to include the IFN␥-responsive element (␥RE), which controls expression of the MIG chemokine gene (43, 44), a third form of IFN␥-sensitive nucleotide regulatory motif. The results demonstrate that IL-4-dependent suppression of IFN␥-induced MIG gene expression is abolished in peritoneal macrophages from mice in which the STAT6 gene has been deleted (45). Both the MIG gene promoter and the ␥RE from the MIG promoter are sensitive to the stimulatory action of IFN␥ and the inhibitory effec...

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Section: Fig 4 Effects Of Ifn␥ and Il-4 On Transcription From The Mmentioning

confidence: 99%

mentioning

confidence: 99%

STAT6 Is Required for the Anti-inflammatory Activity of Interleukin-4 in Mouse Peritoneal Macrophages

Ohmori

Hamilton

1998

Journal of Biological Chemistry

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“…Galectins represent a growing multifunctional superfamily and some of them were found to participate in the adhesion of neutrophils, eosinophils and macrophages through interaction with their ligands, such as CD11b, in a lactose dependent manner [18]. Lactosamine, the basic repeat unit within the backbone of the glycoconjugates, also attracted much interest [19]. Lactose and its derivatives were used in anti-adhesion assays as well as anti-tumor metastasis studies [20,21].…”

mentioning

confidence: 99%

Lactosyl derivatives function in a rat model of severe burn shock by acting as antagonists against CD11b of integrin on leukocytes

Zhao

Hu³

et al. 2008

Glycoconj J

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Severe burn shock remains an unsolved clinical problem with urgent needs to explore novel therapeutic approaches. In this study, the in vivo bioactivity of a series of synthetic lactosyl derivatives (oligosaccharides) was assessed on rats with burn shock to elucidate the underlying mechanisms. Administration of An-2 and Gu-4, two lactosyl derivatives with di- and tetravalent beta-D: -galactopyranosyl-(1-4)-beta-D: -glucopyranosyl ligands, significantly prolonged the survival time (P < 0.05 vs. saline), stabilized blood pressure and ameliorated the injuries to vital organs after burn. Flow chamber assay displayed that An-2 and Gu-4 markedly decreased the adhesion of leukocytes to microvessel endothelial cells. Competitive binding assay showed that a CD11b antibody significantly interrupted the interaction of An-2 and Gu-4 with leukocytes from rats with burn shock. With fluorescent microscopy, we further found that the oligosaccharides were selectively bound to leukocytes and with a colocalization of CD11b on the cell membrane. Interestingly, the lectin domain-deficient form of CD11b failed to bind with An-2 and Gu-4. The results suggest that both An-2 and Gu-4 significantly inhibit the adhesion of leukocytes to endothelial cells by binding to CD11b and thereby exert protective effects on severe burn shock.

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“…Other cells, such as neutrophils, T cells, endothelial cells involved in inflammation, and several epithelial tumor cells, have the machinery to synthesize the sialyl-Le x determinant, a selectin ligand (25)(26)(27). Activated Th1 CD4 T cells, which bind to P-selectin and migrate to inflamed tissue, up-regulate ␣2,3-sialyltransferase (ST3Gal-IV) and ␣1,3-fucosyltransferase FUT7 (26).…”

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confidence: 99%

Tumor Necrosis Factor α Increases the Expression of Glycosyltransferases and Sulfotransferases Responsible for the Biosynthesis of Sialylated and/or Sulfated Lewis x Epitopes in the Human Bronchial Mucosa

Delmotte

Degroote

Lafitte

et al. 2002

Journal of Biological Chemistry

124

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There is increasing evidence that inflammation may affect glycosylation and sulfation of various glycoproteins. The present study reports the effect of tumor necrosis factor ␣ (TNF-␣), a proinflammatory cytokine, on the glycosyl-and sulfotransferases of the human bronchial mucosa responsible for the biosynthesis of Lewis x epitope and of its sialylated and/or sulfated derivatives, which are expressed in human bronchial mucins. Fragments of macroscopically normal human bronchial mucosa were exposed to TNF-␣ at a concentration of 20 ng/ml. TNF-␣ was shown to increase ␣1,3-fucosyltransferase activity as well as expression of the two ␣1,3-fucosyltransferase genes expressed in the human airway, FUT3 and FUT4. It had no influence on ␣1,2-fucosyltransferase activity or FUT2 expression. It also increased ␣2,3-sialyltransferase activity and the expression of ST3Gal-III and, more importantly, ST3Gal-IV and both N-acetylglucosamine 6-O-sulfotransferase and galactose 3-O-sulfotransferase. These results are consistent with the observation of oversialylation and increased expression sialyl-Lewis x epitopes on human airway mucins secreted by patients with severe lung infection such as those with cystic fibrosis, whose airways are colonized by Pseudomonas aeruginosa. However, other cytokines may also be involved in this process.

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Cited by 43 publications

References 87 publications

STAT6 Is Required for the Anti-inflammatory Activity of Interleukin-4 in Mouse Peritoneal Macrophages

STAT6 Is Required for the Anti-inflammatory Activity of Interleukin-4 in Mouse Peritoneal Macrophages

Lactosyl derivatives function in a rat model of severe burn shock by acting as antagonists against CD11b of integrin on leukocytes

Tumor Necrosis Factor α Increases the Expression of Glycosyltransferases and Sulfotransferases Responsible for the Biosynthesis of Sialylated and/or Sulfated Lewis x Epitopes in the Human Bronchial Mucosa

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