Human interleukin‐13 activates the interleukin‐4‐dependent transcription factor NF‐IL4 sharing a DNA binding motif with an interferon‐γ‐induced nuclear binding factor

Köhler, I; Alliger, Peter; Minty, Adrian; Caput, Daniel; Ferrara, Pascual; Höll-Neugebauer, Bärbel; Rank, G.; Rieber, Ernst Peter

doi:10.1016/0014-5793(94)00438-2

Cited by 54 publications

(27 citation statements)

References 31 publications

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“…These data are consistent with previous studies indicating that IL-13 does not induce proliferation of normal human PB T cells or T cell clones (31,46). However, these results are somewhat contradictory to those of a recent study demonstrating that IL-4 and TL-13 activate the same nuclear transcription factor in highly purified human T cells (47). Thus, it remains possible that T cells express functional IL-13 receptor complex, but the IL-13-induced signaling pathway may lack components that are required for the induction of T cell proliferation.…”

Section: Discussionsupporting

confidence: 84%

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The presence of interleukin‐13 in rheumatoid synovium and its antiinflammatory effects on synovial fluid macrophages from patients with rheumatoid arthritis

Isomäki¹,

Luukkainen²,

Toivanen³

et al. 1996

Arthritis & Rheumatism

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Objective. To study the production of interleukin-13 (IL13) in rheumatoid synovium and the effects of recombinant IL-13 on the phenotype and function of synovial fluid (SF) macrophages and T cells derived from patients with rheumatoid arthritis (RA).Methods. The presence of IL-13 in SF was studied using an IL-13-specific enzyme-linked immunosorbent assay (ELISA); the production of IL-13 was studied in SF mononuclear cells (SFMC) by reverse transcriptasepolymerase chain reaction. The effects of recombinant IL-13 on cytokine production by and phenotype of SFMC were evaluated using cytokine-specific ELISAs and flow cytometry, respectively. The effect of IL-13 on the proliferation of SFMC was determined by 3H-thymidine incorporation. The production and the effects of IL-13 were compared with those of IL4.Results. IL-13 was present in 27 of 28 SF samples, and IG13 messenger RNA (mRNA) was detectable in SFMC. Importantly, IL-13 levels were significantly higher than those of IL-4, and IL-13 protein and mRNA were Fxpressed in several samples, although IL-4 synthesis was undetectable. Recombinant IL-13 significantly reduced the production of IL-lP and tumor necrosis factor (Y and the expression of CD16 and CD64 by SF macrophages, whereas the expression of HLA-DR and CD23 was increased. These effects on SF macro- Submitted for publication January 22, 1996; accepted in revised form May 6, 1996. phages were similar to those observed with IL-4, but in contrast to IL-4, IL-13 had no growth-promoting effect on SF T cells.Conclusion. IG13 is consistently present in rheumatoid synovium. The ability of exogenous IL-13 to decrease the production of proinflammatory cytokines by SFMC suggests that it may have therapeutic potential in the treatment of patients with RA.

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Section: Discussionsupporting

confidence: 84%

“…As shown in Table 2, the effects of IL-4 and IL-13 on these 2 cell populations were (31,46). Recently, however, IL-13 was shown to induce phosphorylation of the IL-4-dependent transcription factor NF-IL-4 in highly purified human T cells, suggesting that a functional IL-13 receptor complex is expressed in these cells (47).…”

Section: Isommentioning

confidence: 95%

The presence of interleukin‐13 in rheumatoid synovium and its antiinflammatory effects on synovial fluid macrophages from patients with rheumatoid arthritis

Isomäki¹,

Luukkainen²,

Toivanen³

et al. 1996

Arthritis & Rheumatism

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“…IL-13, a cytokine secreted by activated T cells, is also capable of activating Stat6 under some circumstances and shares many of the biological properties of IL-4 (Kohler et al, 1994;Zurawski and de Vries, 1994). The overlapping functional and biochemical activities of IL-4 and IL-13 can be explained by the fact that their receptors share the IL-4Ra chain (Lin et al, 1995;Zurawski et al, 1995).…”

Section: Stat6 and The Il-4 Receptormentioning

confidence: 99%

The biology of Stat4 and Stat6

2000

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“…Cellular extracts were prepared as described by Jiang and Eberhardt [16]. Gel shift assays were performed as described by Kölher et al [17] with 10-20 μg of proteins and 5xl0 4 -lxl0 5 cpm of the 32 P-labelled probe corresponding to the human CE element from the human Ce control region [18] (5'-GATCCACTTCCCAAGAACAGA-3', the core sequence is underlined). Stat6 containing complexes were confirmed by supershifting with 2 μg of a monoclonal antibody anti-Stat6, M20 (Santa Cruz, CA), added to the binding reaction before EMSA.…”

Section: Binding and Biological Activity Assaysmentioning

confidence: 99%

Cloning of the human IL‐13Rα1 chain and reconstitution with the IL‐4Rα of a functional IL‐4/IL‐13 receptor complex

Miloux¹,

Laurent²,

Bonnin³

et al. 1997

FEBS Letters

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200

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The human homologue of the recently cloned murine IL-13 binding protein (IL-13Ral) was cloned from a cDNA library derived from the carcinoma cell line CAKI-1. The cloned cDNA encodes a 427 amino acid protein with two consensus patterns characteristic of the hematopoietic cytokine receptor family and a short cytoplasmic tail. The human protein is 74% identical to the murine IL-13Ral, and 27% identical to the human IL-13Ra2. CHO cells expressing recombinant hlL13Ral specifically bind IL-13 (Äd~4 nM) but not IL-4. Coexpression of the cloned cDNA with that of IL-4Ra resulted in a receptor complex that displayed high affinity for IL-13 (Κ^ ~ 30 pM), and that allowed cross-competition of IL-13 and IL-4. Electrophoretic mobility shift assay showed that IL-13 and IL-4 were able to activate Stat6 in cells expressing both IL-4Roc and IL-13Ral, while no activation was observed in cells expressing either one or the other alone.

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Human interleukin‐13 activates the interleukin‐4‐dependent transcription factor NF‐IL4 sharing a DNA binding motif with an interferon‐γ‐induced nuclear binding factor

Cited by 54 publications

References 31 publications

The presence of interleukin‐13 in rheumatoid synovium and its antiinflammatory effects on synovial fluid macrophages from patients with rheumatoid arthritis

The presence of interleukin‐13 in rheumatoid synovium and its antiinflammatory effects on synovial fluid macrophages from patients with rheumatoid arthritis

The biology of Stat4 and Stat6

Cloning of the human IL‐13Rα1 chain and reconstitution with the IL‐4Rα of a functional IL‐4/IL‐13 receptor complex

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