Expression and responsiveness of human interleukin-18 receptor (IL-18R) on hematopoietic cell lines

Nakamura, Shuji; Otani, Takeshi; Okura, Ryusuke; Ijiri, Yoshihiro; Motoda, Ryuichi; Kurimoto, Masashi; Orita, Kunzo

doi:10.1038/sj.leu.2401789

Cited by 50 publications

(42 citation statements)

References 33 publications

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“…IL-18 may mediate its effects directly by augmentation of IFN-γ production 6 10 23 24 or by enhancement of the expression of the IL-12R complex, thereby potentiating the effects of IL-12 25. While many studies have focused attention on the regulation of the IL-12R during Th cell differentiation, fewer have focused on regulation of the IL-18R 24 26 27 28 29. It has been widely assumed that the IL-18Rα is expressed only after T cell activation as the IL-18Rα could readily be detected on fully differentiated murine Th1 cells, but not on Th2 cells, either at the mRNA level or at the cell surface 22 23 24 26.…”

Section: Discussionmentioning

confidence: 99%

Regulation of Interleukin (Il)-18 Receptor α Chain Expression on Cd4+ T Cells during T Helper (Th)1/Th2 Differentiation

Smeltz

Chen

Hu‐Li

et al. 2001

The Journal of Experimental Medicine

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Interleukin (IL)-18 has been well characterized as a costimulatory factor for the induction of IL-12–mediated interferon (IFN)-γ production by T helper (Th)1 cells, but also can induce IL-4 production and thus facilitate the differentiation of Th2 cells. To determine the mechanisms by which IL-18 might regulate these diametrically distinct immune responses, we have analyzed the role of cytokines in the regulation of IL-18 receptor α chain (IL-18Rα) expression. The majority of peripheral CD4+ T cells constitutively expressed the IL-18Rα. Upon antigen stimulation in the presence of IL-12, marked enhancement of IL-18Rα expression was observed. IL-12–mediated upregulation of IL-18Rα required IFN-γ. Activated CD4+ T cells that expressed low levels of IL-18Rα could produce IFN-γ when stimulated with the combination of IL-12 and IL-18, while CD4+ cells which expressed high levels of IL-18Rα could respond to IL-18 alone. In contrast, T cell stimulation in the presence of IL-4 resulted in a downregulation of IL-18Rα expression. Both IL-4−/− and signal transducer and activator of transcription (Stat)6−/− T cells expressed higher levels of IL-18Rα after TCR stimulation. Furthermore, activated T cells from Stat6−/− mice produced more IFN-γ in response to IL-18 than wild-type controls. Thus, positive/negative regulation of the IL-18Rα by the major inductive cytokines (IL-12 and IL-4) determines the capacity of IL-18 to polarize an immune response.

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Section: Discussionmentioning

confidence: 99%

Regulation of Interleukin (Il)-18 Receptor α Chain Expression on Cd4+ T Cells during T Helper (Th)1/Th2 Differentiation

Smeltz

Chen

Hu‐Li

et al. 2001

The Journal of Experimental Medicine

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“…Thus, IL-18 mRNA has been detected in malignant cells from colon and ovarian carcinoma (25, 26), mantle cell lymphoma (27), and skin cancer (28). IL-18R␣ expression has been reported in different hematopoietic cell lines, part of which were derived from patients with lymphoproliferative or myeloproliferative disorders, but not in primary tumor cells (29). EBV infection has been shown to up-regulate IL-18 expression in secondary lymphoid tissues from patients with infectious mononucleosis and, at a lesser extent, posttransplant lymphoproliferative disorder (22).…”

Section: Introductionmentioning

confidence: 99%

Heterogeneous Expression of Interleukin-18 and Its Receptor in B-Cell Lymphoproliferative Disorders Deriving from Naive, Germinal Center, and Memory B Lymphocytes

Airoldi¹,

Raffaghello²,

Cocco³

et al. 2004

Clinical Cancer Research

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“…We have examined these two cell lines with regard to the level of IL-18R␣/␤ expression using flow cytometry and receptor binding assay. Previous data showed that TNF-␣ could significantly increase the response of KG-1 cells to IL-18 in IFN-␥ production, suggesting that TNF-␣ might upregulate the expression of IL-18R␣ and/or IL-18R␤ (18). Therefore, we also analyzed TNF-␣-primed KG-1 cells for receptor expression and IL-18 binding.…”

Section: Expression Of Il-18r␣ and ␤ Subunits And Binding Of Il-18mentioning

confidence: 97%

“…Among the many cell lines tested, L428 exhibited the strongest level of total IL-18 binding, but failed to secret IFN-␥ in response to IL-18 (12,18), and KG-1 cells produced IFN-␥ in response to IL-18 stimulation (18). However the IL-18R expression patterns (i.e., whether they express only IL-18R␣ or both IL-18R␣ and -␤, and the receptor numbers and affinities) on these cells have not been assessed in detail.…”

Section: Expression Of Il-18r␣ and ␤ Subunits And Binding Of Il-18mentioning

confidence: 99%

IL-18 Receptor β-Induced Changes in the Presentation of IL-18 Binding Sites Affect Ligand Binding and Signal Transduction

Sakorafas

Miller

et al. 2003

The Journal of Immunology

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IL-18 is a pleiotropic proinflammatory cytokine that is involved in induction of inflammatory mediators, regulation of the cytotoxic activity of NK cells and T cells, and differentiation and activation of both Th1 and Th2 cells. IL-18 signals through its specific cell surface receptor IL-18R, which comprises two subunits: IL-18Rα and IL-18Rβ. IL-18Rα alone has a weak affinity for IL-18 binding, while the IL-18Rα/β complex has a high affinity. By using several anti-IL-18 mAbs and IL-18 binding protein, we have examined whether these site-specific inhibitors could block the binding of IL-18 to IL-18Rα and to the IL-18Rα/β complex. Here we show that IL-18 binding to IL-18Rα was inhibited by a neutralizing mAb, 125-2H, while binding of IL-18 to the α/β receptor complex was not. This suggests that IL-18Rβ-induced conformational changes may occur in IL-18Rα upon dimerization, leading to changes in the presentation of IL-18 binding sites. Epitope mapping of 125-2H using human-mouse IL-18 chimeras identified a region in IL-18 that was required for 125-2H recognition. This region, as examined by IL-18R binding and functional analysis, appeared to be critical for triggering signal transduction through the heterodimeric receptor.

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Expression and responsiveness of human interleukin-18 receptor (IL-18R) on hematopoietic cell lines

Abstract: Interleukin-18 (IL-18

Cited by 50 publications

References 33 publications

Regulation of Interleukin (Il)-18 Receptor α Chain Expression on Cd4+ T Cells during T Helper (Th)1/Th2 Differentiation

Regulation of Interleukin (Il)-18 Receptor α Chain Expression on Cd4+ T Cells during T Helper (Th)1/Th2 Differentiation

Heterogeneous Expression of Interleukin-18 and Its Receptor in B-Cell Lymphoproliferative Disorders Deriving from Naive, Germinal Center, and Memory B Lymphocytes

IL-18 Receptor β-Induced Changes in the Presentation of IL-18 Binding Sites Affect Ligand Binding and Signal Transduction

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