Interleukin‐1 receptor accessory protein interacts with the type II interleukin‐1 receptor

Malinowsky, David; Lundkvist, Johan; Layé, Sophie; Bartfai, Tamás

doi:10.1016/s0014-5793(98)00467-0

Cited by 69 publications

(46 citation statements)

References 18 publications

(23 reference statements)

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“…In addition the IL-1RAcP, which is also expressed on microglial cells (Fig. 2), may increase the affinity of IL-1 for IL-1RII as it has been reported that IL-1RAcP associates with IL-1RII (Malinowsky et al 1998). IL-1RII can be shed from the membrane (Sims et al 1993) and, as a soluble form of IL-1RAcP has been described recently (Jensen et al 2000), these two proteins could act as a soluble complex, thus inhibiting actions of released IL-1.…”

Section: Discussionmentioning

confidence: 83%

Expression of interleukin‐1 receptors and their role in interleukin‐1 actions in murine microglial cells

Pinteaux

Parker

Rothwell

et al. 2002

Journal of Neurochemistry

154

107

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Interleukin (IL)-1 is an important mediator of acute brain injury and inflammation, and has been implicated in chronic neurodegeneration. The main source of IL-1 in the CNS is microglial cells, which have also been suggested as targets for its action. However, no data exist demonstrating expression of IL-1 receptors [IL-1 type-I receptor (IL-1RI), IL-1 type-II receptor (IL-1RII) and IL-1 receptor accessory protein (IL-1RAcP)] on microglia. In the present study we investigated whether microglia express IL-1 receptors and whether they present target or modulatory properties for IL-1 actions. RT-PCR analysis demonstrated lower expression of IL-1RI and higher expression of IL-1RII mRNAs in mouse microglial cultures compared with mixed glial or pure astrocyte cultures. Bacterial lipopolysaccharide (LPS) caused increased expression of IL-1RI, IL-1RII and IL-1RAcP mRNAs, induced the release of IL-1b, IL-6 and prostaglandin-E 2 (PGE 2 ), and activated nuclear factor jB (NF-jB) and the mitogen-activated protein kinases (MAPKs) p38, and extracellular signal-regulated protein kinase (ERK1/2), but not c-Jun N-terminal kinase (JNK) in microglial cultures. In comparison, IL-1b induced the release of PGE 2 , IL-6 and activated NF-jB, p38, JNK and ERK1/2 in mixed glial cultures, but failed to induce any of these responses in microglial cell cultures. IL-1b also failed to affect LPS-primed microglial cells. Interestingly, a neutralizing antibody to IL-1RII significantly increased the concentration of IL-1b in the medium of LPS-treated microglia and exacerbated the IL-1b-induced IL-6 release in mixed glia, providing the first evidence that microglial IL-1RII regulates IL-1b actions by binding excess levels of this cytokine during brain inflammation. Keywords: interleukin 1 receptors, interleukin 1 signaling, microglial cells, mitogen-activated protein kinase, nuclear factor kappa B.

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Section: Discussionmentioning

confidence: 83%

Expression of interleukin‐1 receptors and their role in interleukin‐1 actions in murine microglial cells

Pinteaux

Parker

Rothwell

et al. 2002

Journal of Neurochemistry

154

107

View full text Add to dashboard Cite

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“…As shown in Figure 2D, overexpression of sIL-1RAcP likely formed complexes on the cell surface of IL-1␤ bound to type II receptors. This complex as the type II receptor decoy mechanism was first proposed by Malinowsky et al (25) and Lang et al (26), and accounts for the ability of sIL-1RAcP to reduce B lymphocyte activation. It is thus likely that low levels of type II receptors on T lymphocytes prevent suppression of T lymphocytes in vivo and in vitro by sIL-1RAcP.…”

Section: Cell Selectivity Of Decoy Il-1rmentioning

confidence: 89%

“…This receptor, which lacks a cytoplasmic domain and cannot participate in signal transduction, functions as a decoy receptor by competitive binding to IL-1␤ (24) ( Figure 2B). The type II receptor can also form an inactive complex with the IL-1RAcP ( Figure 2B), preventing the cell from participating in signal transduction (25,26).…”

Section: What Accounts For the Differences Between Overexpression Of mentioning

confidence: 99%

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The many worlds of reducing interleukin‐1

Dinarello¹

2005

Arthritis & Rheumatism

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“…However, the IL-1RII can also indirectly determine the availability of the IL-1RAcP. The amount of IL-1RII expression on the membrane determines the sensitivity of the cell toward IL-1, and membrane IL-1RAcP is able to interact with the IL-1RII (18,47). Therefore, abundant expression of the IL-1RII will not only lead to scavenging of IL-1, but will also reduce the available IL-1RAcP to form a signaling complex with the type I receptor, shifting the balance in favor of the sIL-1RAcP for receptor competition with the IL-1RAcP for formation of receptor complexes with IL-1RI.…”

Section: Discussionmentioning

confidence: 99%

Soluble interleukin‐1 receptor accessory protein ameliorates collagen‐induced arthritis by a different mode of action from that of interleukin‐1 receptor antagonist

Smeets¹,

Joosten²,

Arntz³

et al. 2005

Arthritis & Rheumatism

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Objective. To discern the mode of interleukin-1 (IL-1) inhibition of soluble IL-1 receptor accessory protein (sIL-1RAcP) by comparison with IL-1 receptor antagonist (IL-1Ra) in arthritis.Methods. Adenoviral vectors encoding either sIL1RAcP or IL-1Ra were administered systemically before onset of collagen-induced arthritis in DBA/1 mice. Antibovine type II collagen IgG and IL-6 were quantified in serum. Proliferative response of splenic T cells was determined in the presence of sIL-1RAcP or IL-1Ra. The effect on IL-1 inhibition of recombinant sIL-1RAcP and IL-1Ra was further examined in vitro, using NF-B luciferase reporter cell lines. Quantitative polymerase chain reaction was used to determine the relative messenger RNA expression of the IL-1 receptors.Results. Adenoviral overexpression of both sIL1RAcP and IL-1Ra resulted in amelioration of the collagen-induced arthritis. Both IL-1 antagonists reduced the circulating levels of antigen-specific IgG2a antibodies, but only IL-1Ra was able to inhibit lymphocyte proliferation. By using purified lymphocyte populations derived from NF-B reporter mice, we showed that sIL-1RAcP inhibits IL-1-induced NF-B activity in B cells but not T cells, whereas IL-1Ra inhibited IL-1 on both cell types. A study in a panel of NF-B luciferase reporter cells showed that the sIL-1RAcP inhibits IL-1 signaling on cells expressing either low levels of membrane IL-1RAcP or high levels of IL-1RII.Conclusion. We show that the sIL-1RAcP ameliorated experimental arthritis without affecting T cell immunity, in contrast to IL-1Ra. Our results provide data in support of receptor competition by sIL-1RAcP as an explanation for the different mode of IL-1 antagonism in comparison with IL-1Ra.

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Interleukin‐1 receptor accessory protein interacts with the type II interleukin‐1 receptor

Cited by 69 publications

References 18 publications

Expression of interleukin‐1 receptors and their role in interleukin‐1 actions in murine microglial cells

Expression of interleukin‐1 receptors and their role in interleukin‐1 actions in murine microglial cells

The many worlds of reducing interleukin‐1

Soluble interleukin‐1 receptor accessory protein ameliorates collagen‐induced arthritis by a different mode of action from that of interleukin‐1 receptor antagonist

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