Selectivity Release of the Type Ii Decoy Il-1 Receptor

Orlando, Simone; Polentarutti, Nadia; Mantovani, Alberto

doi:10.1006/cyto.1999.0601

Cited by 13 publications

(5 citation statements)

References 35 publications

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“…IL-1 (IL-1Α and IL-1Β), a multifunctional cytokine involved in a host of pro-inflammatory responses and diseases [50], affects target cells through two distinct types of transmembrane receptors, IL1R1 and IL1R2. IL1R1 transduces the signal from IL-1, while IL1R2 acts as a decoy receptor to subtract IL-1 from ILR1 [51,52]. The ratio between the expression of IL1R1 and IL1R2 has been shown to be the central factor in determining the responsiveness of a cell to IL-1 [53].…”

Section: Discussionmentioning

confidence: 99%

Transcriptional profiles during the differentiation and maturation of monocyte-derived dendritic cells, analyzed using focused microarrays

Wei-xue

Fei

Zhu³

et al. 2009

Cellular and Molecular Biology Letters

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Dendritic cells (DC) are professional antigen-presenting cells capable of initiating primary immune responses. They have been intensively studied and are used in both basic immunology research and clinical immunotherapy. However, the genetic pathways leading to DC differentiation and maturation remain poorly understood. Using focused microarrays with oligonucletotide probes for 120 genes encoding co-stimulatory molecules, chemokines, chemokine receptors, cytokines, cytokine receptors, TLRs, and several other related molecules, we analyzed the kinetics of gene expression for the overall differentiation process of monocytes into mature DC. In parallel, we compared the transcriptional profiles in DC maturation in the presence of LPS, TNF-α or trimeric CD40L. We found similar transcriptional profiles for early immature DC and immature DC, respectively generated by culturing monocytes with GM-CSF and IL-4 for three or six days. We identified sets of common and stimulispecific genes, the expression of which changed following stimulation with LPS, TNF-α or CD40L. A dynamic analysis of the entire DC differentiation and maturation process showed that some important inflammatory and constitutive chemokines are transcribed in both immature and mature DC. light on the transcriptional kinetics of DC differentiation and maturation, and this method may also prove useful for identifying novel marker genes involved in DC functions.

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Section: Discussionmentioning

confidence: 99%

Transcriptional profiles during the differentiation and maturation of monocyte-derived dendritic cells, analyzed using focused microarrays

Wei-xue

Fei

Zhu³

et al. 2009

Cellular and Molecular Biology Letters

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“…Soluble IL-1RII has typically been described as a 45-to 47-kDa protein that is generated via proteolytic cleavage and release of the IL-1RII extracellular domain (20,22,23). This is supported by the inhibition of both slow and rapid IL-1RII shedding by hydroxamic acid-based zinc metalloprotease inhibitors (20).…”

Section: Shedding Of the Type II Il-1 Decoy Receptor Requires A Multimentioning

confidence: 99%

Shedding of the Type II IL-1 Decoy Receptor Requires a Multifunctional Aminopeptidase, Aminopeptidase Regulator of TNF Receptor Type 1 Shedding

Cui

Rouhani

Hawari

et al. 2003

The Journal of Immunology

168

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Proteolytic cleavage of the extracellular domain of the type II IL-1 decoy receptor (IL-1RII) generates soluble IL-1-binding proteins that prevent excessive bioactivity by binding free IL-1. In this study we report that an aminopeptidase, aminopeptidase regulator of TNFR1 shedding (ARTS-1), is required for IL-1RII shedding. Coimmunoprecipitation experiments demonstrate an association between endogenous membrane-associated ARTS-1 and a 47-kDa IL-1RII, consistent with ectodomain cleavage of the membrane-bound receptor. A direct correlation exists between ARTS-1 protein expression and IL-1RII shedding, as cell lines overexpressing ARTS-1 have increased IL-1RII shedding and decreased membrane-associated IL-1RII. Basal IL-1RII shedding is absent from ARTS-1 knockout cell lines, demonstrating that ARTS-1 is required for constitutive IL-1RII shedding. Similarly, PMA-mediated IL-1RII shedding is almost entirely ARTS-1-dependent. ARTS-1 expression also enhances ionomycin-induced IL-1RII shedding. ARTS-1 did not alter levels of membrane-associated IL-1RI or IL-1R antagonist release from ARTS-1 cell lines, which suggests that the ability of ARTS-1 to promote shedding of IL-1R family members may be specific for IL-1RII. Further, increased IL-1RII shedding by ARTS-1-overexpressing cells attenuates the biological activity of IL-1β. We conclude that the ability of ARTS-1 to enhance IL-1RII shedding represents a new mechanism by which IL-1-induced cellular events can be modulated. As ARTS-1 also promotes the shedding of the structurally unrelated 55-kDa, type I TNF receptor and the IL-6R, we propose that ARTS-1 may play an important role in regulating innate immune and inflammatory responses by increasing cytokine receptor shedding.

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“…The physiological implications of receptor cleavage are diverse. In some cases, the soluble receptor may function as a decoy receptor, which inhibits the activities mediated by binding of their ligands [8,9]. Membrane receptor cleavage can also downregulate ligand signalling by decreasing the amount of intact receptor localised on the cell membrane [10].…”

Section: Introductionmentioning

confidence: 99%

Sequential cleavage of insulin receptor by calpain 2 and γ-secretase impairs insulin signalling

et al. 2016

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Selectivity Release of the Type Ii Decoy Il-1 Receptor

Cited by 13 publications

References 35 publications

Transcriptional profiles during the differentiation and maturation of monocyte-derived dendritic cells, analyzed using focused microarrays

Transcriptional profiles during the differentiation and maturation of monocyte-derived dendritic cells, analyzed using focused microarrays

Shedding of the Type II IL-1 Decoy Receptor Requires a Multifunctional Aminopeptidase, Aminopeptidase Regulator of TNF Receptor Type 1 Shedding

Sequential cleavage of insulin receptor by calpain 2 and γ-secretase impairs insulin signalling

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