IL-1 Receptor Accessory Protein and ST2 Comprise the IL-33 Receptor Complex

Chackerian, Alissa A.; Oldham, Elizabeth R.; Murphy, Erin; Schmitz, Jochen; Pflanz, Stefan; Kastelein, Robert A.

doi:10.4049/jimmunol.179.4.2551

Cited by 466 publications

(398 citation statements)

References 23 publications

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“…IL-33 is produced as a 30 kDa protein. After binding to the long form of the ST2 receptor (ST2L), IL-33 recruits IL-1RAcP, the common co-receptor for IL-1α and IL-1β, to activate signaling pathways, including NF-κB and MAP kinases [15][16][17].…”

Section: Introductionmentioning

confidence: 99%

IL-33 is expressed in human osteoblasts, but has no direct effect on bone remodeling

et al. 2011

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1 IL-33 is expressed in human osteoblasts, but has no direct effect on bone remodelingsuggested that expression of IL-33, in contrast to that of IL-1β, is not repressed by PPARγ, likely explaining why IL-33, but not IL-1β, is expressed in adipocytes. The IL-33 receptor ST2L is not constitutively expressed in human bone marrow stromal cells, osteoblasts or CD14-positive monocytes, and IL-33 has no effect on these cells. In addition, although ST2L mRNA is induced by TNF-α and IL-1β in bone marrow stromal cells, IL-33 has the same effects as TNF-α and IL-1β, and, therefore, the biological activity of IL-33 may be redundant in this system. In agreement with this hypothesis, MC3T3-E1 osteoblast-like cells constitutively express ST2L mRNA, and in these cells IL-33 and TNF-α/IL-1β similarly decrease osteocalcin RNA levels in these cells. In conclusion, our results suggest that IL-33 has no direct effects on normal bone remodeling.

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Section: Introductionmentioning

confidence: 99%

IL-33 is expressed in human osteoblasts, but has no direct effect on bone remodeling

et al. 2011

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“…ST2 is expressed on mast cells (18), LPS-activated macrophages (7), and Th2 lymphocytes (19) and exists as transmembrane (ST2L) and soluble (sST2) isoforms generated by alternative splicing (20). IL-33 has been shown to induce the secretion of both proinflammatory and antiinflammatory cytokines and chemokines from mast cells, eosinophils, and Th2 lymphocytes (16,21,22). However, the influence of IL-33 on macrophages has not yet been studied.…”

mentioning

confidence: 99%

“…These molecules are shared by other TLR-dependent pathways, notably the CD14/MD2/TLR-4 complex, which is triggered by LPS. Recently, the IL-1R accessory protein IL-1RAcP, which is also involved in IL-1 signaling, was found to heterodimerize with ST2 when IL-33 is bound to ST2 (16,17). ST2 is expressed on mast cells (18), LPS-activated macrophages (7), and Th2 lymphocytes (19) and exists as transmembrane (ST2L) and soluble (sST2) isoforms generated by alternative splicing (20).…”

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confidence: 99%

IL-33 Enhances Lipopolysaccharide-Induced Inflammatory Cytokine Production from Mouse Macrophages by Regulating Lipopolysaccharide Receptor Complex

Espinassous

Garcia-de-Paco²,

García-Verdugo³

et al. 2009

The Journal of Immunology

142

115

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Bacterial LPS triggers monocytes and macrophages to produce several inflammatory cytokines and mediators. However, once exposed to LPS, they become hyporesponsive to a subsequent endotoxin challenge. This phenomenon is defined as LPS desensitization or tolerance. Previous studies have identified some components of the biochemical pathways involved in negative modulation of LPS responses. In particular, it has been shown that the IL-1R-related protein ST2 could be implicated in LPS tolerance. The natural ligand of ST2 was recently identified as IL-33, a new member of the IL-1 family. In this study, we investigated whether IL-33 triggering of ST2 was able to induce LPS desensitization of mouse macrophages. We found that IL-33 actually enhances the LPS response of macrophages and does not induce LPS desensitization. We demonstrate that this IL-33 enhancing effect of LPS response is mediated by the ST2 receptor because it is not found in ST2 knockout mice. The biochemical consequences of IL-33 pretreatment of mouse macrophages were investigated. Our results show that IL-33 increases the expression of the LPS receptor components MD2 (myeloid differentiation protein 2) and TLR-4, the soluble form of CD14 and the MyD88 adaptor molecule. In addition, IL-33 pretreatment of macrophages enhances the cytokine response to TLR-2 but not to TLR-3 ligands. Thus, IL-33 treatment preferentially affects the MyD88-dependent pathway activated by the TLR.

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“…It is found in various cells included fibroblasts, bronchial and epithelial cells, endothelial cells, and some immune cells, including macrophages and dendritic cells (Kakkar and Lee 2008). IL-33 is a multifunctional cytokine in immune regulation that activates Th1 cells, Th2 cells, CD8+T cells and NK cells (Chackerian et al, 2007;Bourgeois et al, 2009;Liew, et al, 2010;Bonilla et al, 2012). Accumulated data also demonstrated that immune cells play important role in tumor progress and prognosis (Dobrzanski et al, 2006;Williams and Bevan 2007).…”

Section: Introductionmentioning

confidence: 99%

Correlations Between Serum IL33 and Tumor Development: a Meta-analysis

Chen

Huang²,

Li³

et al. 2014

Asian Pacific Journal of Cancer Prevention

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Background: Interleukin-33 (IL-33) has recently been implicated in tumor development. Methods: Data was obtained from PubMed, EMBASE, Clinical trial, Cochrane Library, Web of Science, CNKI and Wanfang databases. After quality assessment and data extraction, a meta-analysis was performed using Review Manager 5. 2 software. Results: There were eight documents included in this meta-analysis. The results showed IL33 levels to be higher in tumor patients than that in health people, but no correlations tumor stage, metastasis and survival time of tumor patients were evident. Conclusion: IL33 may be useful as an alarm factor in tumor detection and prognosis.

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IL-1 Receptor Accessory Protein and ST2 Comprise the IL-33 Receptor Complex

Cited by 466 publications

References 23 publications

IL-33 is expressed in human osteoblasts, but has no direct effect on bone remodeling

IL-33 is expressed in human osteoblasts, but has no direct effect on bone remodeling

IL-33 Enhances Lipopolysaccharide-Induced Inflammatory Cytokine Production from Mouse Macrophages by Regulating Lipopolysaccharide Receptor Complex

Correlations Between Serum IL33 and Tumor Development: a Meta-analysis

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