Interleukin-18 Activates NF-κB in Murine T Helper Type 1 Cells

Matsumoto, Shûji; Tsuji-Takayama, Kazue; Aizawa, Yasushi; Koide, Kazunori; Takeuchi, Makoto; Ohta, Toshio; Kurimoto, Masashi

doi:10.1006/bbrc.1997.6665

Cited by 188 publications

(106 citation statements)

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“…In this study, we showed that IL-18-induced up-regulation of SDF-1␣/CXCL12, MCP-1/CCL2, and VEGF was mediated via NF B. It has previously been shown that most of the signaling pathways activated by IL-18 converge on NF B (26,45), indicating that NF B is critical in IL-18-induced secretion of proinflammatory cytokines in chronic inflammatory diseases such RA. We found a significant increase of p65 NF B nuclear localization in RA ST fibroblasts stimulated for 30 minutes with IL-18, compared with unstimulated cells (Figure 4C).…”

Section: Il-18 and Angiogenic Factorsmentioning

confidence: 56%

Interleukin‐18 induces angiogenic factors in rheumatoid arthritis synovial tissue fibroblasts via distinct signaling pathways

Amin

Mansfield

Pákozdi

et al. 2007

Arthritis & Rheumatism

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Objective. Interleukin-18 (IL-18) is a proinflammatory cytokine implicated in the pathogenesis of rheumatoid arthritis (RA). This study was undertaken to examine the role of IL-18 in up-regulating secretion of the angiogenic factors stromal cell-derived factor 1␣ (SDF-1␣)/CXCL12, monocyte chemoattractant protein 1 (MCP-1)/CCL2, and vascular endothelial growth factor (VEGF) in RA synovial tissue (ST) fibroblasts, and the underlying signaling mechanisms involved.Methods. We used enzyme-linked immunosorbent assays, Western blotting, and chemical inhibitors/ antisense oligodeoxynucleotides to signaling intermediates to assess the role of IL-18.Results.

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Section: Il-18 and Angiogenic Factorsmentioning

confidence: 56%

Interleukin‐18 induces angiogenic factors in rheumatoid arthritis synovial tissue fibroblasts via distinct signaling pathways

Amin

Mansfield

Pákozdi

et al. 2007

Arthritis & Rheumatism

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“…COS-1 cells were transfected by electroporation with expression constructs and harvested after 72 h of incubation as described previously (12). Using the transfected COS-1 cells as targets, binding assays and NF-B gel shift assays were performed (13).…”

Section: Il-1rrp Expression Plasmid and Transfection Of Cos-1 Cellsmentioning

confidence: 99%

Purification and Characterization of the Human Interleukin-18 Receptor

Torigoe

Ushio

Okura

et al. 1997

Journal of Biological Chemistry

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454

285

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Interleukin (IL)-18 was identified as a molecule that induces IFN-␥ production and enhances NK cell cytotoxicity. In this paper, we report upon the purification and characterization of human IL-18 receptor (hIL-18R). We selected the Hodgkin's disease cell line, L428, as the most strongly hIL-18R-expressing cell line based on the results of binding assays. Murine interleukin-18 (mIL-18) 1 was identified in the livers of mice sequentially injected with heat-killed Propionibacterium acnes and with lipopolysaccharide (1). Murine IL-18 cDNA was cloned from murine liver mRNA, and the factor was provisionally termed IFN-␥-inducing factor because it was first identified as an IFN-␥ inducer in mice. Consequently, human interleukin-18 (hIL-18) was cloned from normal human liver mRNA (2). IL-18 is a non-N-linked, glycosylated, 18.3-kDa cytokine in its mature form and exhibits biologic activities in the monomeric form.IL-18 has been found to have a variety of biologic actions, including the stimulation of the proliferation of activated T cells, enhancement of the lytic activity of NK cells, induction of interferon-␥ (IFN-␥), and granulocyte-macrophage colony-stimulating factor production by activated T cells and promotion of Th1-type helper (Th1) clone responses (1-4). It has also been reported that IL-18 inhibits osteoclast-like multinucleated cell formation in co-cultures of osteoblasts and hemopoietic cells of spleen or bone marrow origin (5). Thus, it is very obvious that IL-18 plays an important role in the immune system.IL-18 shares some of its biologic activities with IL-12, although the primary structures of the two cytokines show no homology (2). In addition, in the experiments using murine Th1 clones and enriched human T cells, IL-18 and IL-12 acted on the T cells synergistically to induce IFN-␥ production (1, 4). Interestingly, the amino acid sequence of IL-18 includes the IL-1 signature-like sequence (2) and has been shown to have 15% homology at the amino acid level with the IL-1␤ protein, but does not bear significant functional resemblance to the IL-1 family (2).The identification of the receptor for IL-18 is important for investigation of the physiological role of IL-18 in nature. In this report, we describe the purification and identification of hIL-18R from a Hodgkin's disease-derived cell line, L428, and present some characterization of this molecule. EXPERIMENTAL PROCEDURES Cell Lines and ReagentsC5/MJ, CCRF-HSB-2, HPB-ALL, JM, MOLT-3, MOLT-4, MOLT-16, PEER, SKW-3 (human T cell leukemia), ARH-77, BALL-1 (human B cell leukemia), KG-1, HL-60, U-937 (human myelomonocytic cell leukemia), NALM-16, HEL (human non-T, non-B cell leukemia), and L-428 and HDLM (human Hodgkin's disease) cell lines were maintained in culture at 37°C, in a 5% CO 2 air mixture in RPMI 1640 medium supplemented with 10% heat-inactivated fetal bovine serum (BioWhittaker Inc.). Recombinant human IL-1␤ (R&D Systems) and 125 -I-IL-1␤ (Amersham) were obtained commercially. Recombinant IL-18Recombinant human IL-18 (rhIL-18) was produced by cu...

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“…The rationale of these studies was based on the well-established observation that IFN-␥ contributes to ␤-cell death. In addition, IL-18 increases Fas ligand expression [11,13] and NF-B activation [9,10]. Expression of IL-18 transcripts occurred with the onset of insulitis in the NOD mouse [16].…”

Section: Il-18 and Insulin-dependent Diabetes Mellitusmentioning

confidence: 99%