Interleukin 1 signaling occurs exclusively via the type I receptor.

Sims, John E.; Gayle, Margit; Slack, Jennifer L.; Alderson, Mark R.; Bird, Timothy A.; Giri, Judith G.; Colotta, Francesco; Re, Fabio; Mantovani, Alberto; Shanebeck, Kurt

doi:10.1073/pnas.90.13.6155

Cited by 540 publications

(274 citation statements)

References 42 publications

(14 reference statements)

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“…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. A neutralizing antibody to IL-1RII increased the level of IL-1b in the culture medium of LPS-treated microglia (Fig.…”

Section: Discussionmentioning

confidence: 96%

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

151

106

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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: 96%

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

151

106

View full text Add to dashboard Cite

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“…18 The cloning and characterisation of the two IL-1 receptors (type 1 and 2) 19 has revealed the IL-1 receptor type 2 to function as an IL-1 binding protein that acts as a competitive decoy, lacking the cytoplasmic residues necessary for intracellular signalling. 20 Three structurally related ligands can bind to the IL-1 receptors: IL-1a and the more abundant IL-1b functioning as agonists, and IL1Ra as an antagonist that results in no intracellular signalling.…”

Section: Introductionmentioning

confidence: 99%

Extended haplotypes and linkage disequilibrium in the IL1R1–IL1A–IL1B–IL1RN gene cluster: association with knee osteoarthritis

et al. 2004

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The interleukin-1 gene cluster is a key regulator in a number of chronic disease processes. We explored the linkage between nine polymorphic loci in the IL1R1 promoter, eight in the IL1A-IL1B-IL1RN gene complex, and their association with osteoarthritis (OA), a common complex disease associated with low-level inflammation. Using 195 healthy controls, we identified eight novel polymorphisms in the IL1R1 exon 1A region. We found limited LD between IL1R1 and the IL1A-IL1B-IL1RN cluster, although LD within these two individual groups was high. To test association with knee OA, we genotyped 141 patients from Bristol (UK) at the 17 loci. IL1R1 promoter haplotypes showed no association with disease. However, within the IL1A-IL1B-IL1RN complex, we identified a common haplotype conferring a four-fold risk of OA (P ¼ 0.00043; P c ¼ 0.0043) and one IL1B-IL1RN haplotype conferring a four-fold reduced risk (P ¼ 0.0036; P c ¼ 0.029). To replicate these associations, we subsequently examined 163 knee OA patients from London. Here, the effects of the haplotypes were confirmed: the risk IL1A-IL1B-IL1RN haplotype conferred a two-fold risk of OA (P ¼ 0.02), and the protective IL1B-IL1RN haplotype conferred a fivefold reduced risk of OA (P ¼ 0.0000008). These results may help to explain the genome-wide scan linkage data and functional observations concerning association between IL-1 and OA.

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“…6,7 The interleukin 1 type 1 receptor (IL1-RI) (MIM 147810) is the signal-transducing receptor for IL-1. 8 The receptor is found on most cells, including T lymphocytes and beta cells. The regulation of the IL-1 receptor gene expression is likely to play a major role in controlling the effects of IL-1 since very few receptors are required for IL-1 signalling.…”

Section: Introductionmentioning

confidence: 99%

Characterization of new polymorphisms in the 5′UTR of the human interleukin-1 receptor type 1 (IL1R1) gene: linkage to type 1 diabetes and correlation to IL-1RI plasma level

et al. 2000

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The human interleukin-1 type I receptor (IL-1RI) is the signal transducing receptor for IL-1, a principal proinflammatory cytokine, which is cytotoxic to pancreatic islet beta cells. The IL-1RI gene, IL1R1, maps to chromosome 2q12. We have previously examined part of the IL1R1 promoter region and in the present study we further characterized the promoter region demarcating exon 1B and 1C by sequencing and mutation scanning. New sequence was obtained 1762 bp upstream and 1609 bp downstream the known region. Within this sequence, we identified four frequent single nucleotide polymorphisms (SNPs). PCR-based RFLP assays were established and three of the polymorphisms were typed in a Danish Type 1 (insulin-dependent) diabetes mellitus (T1DM) family collection comprising 103 simplex and 150 sib-pair affected families. Linkage was evaluated by the sib-TDT (transmission disequilibrium test). One of the polymorphisms, defined by a HinfI RFLP assay, demonstrated linkage to T1DM, P(sTDT) = 0.026. Random transmission was observed to unaffected offspring from heterozygous parents, P = 0.87. No evidence for positive linkage was seen for the other tested polymorphisms, P = 0.14 and P = 0.21, respectively. To evaluate the possible functional significance of the HinfI polymorphism, we measured circulating IL-1RI plasma level in 30 T1DM patients and in 30 control subjects -10 with each genotype in both groups. Significant differences in plasma levels in relation to genotype -independent of disease status -were found (P = 0.04). In both diabetic and non-diabetic subjects, the wt/wt genotype correlated with the highest IL-1RI plasma level, whereas the plasma levels were lowest for the mt/mt genotype. Genes and Immunity (2000) 1, 495-500.

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Interleukin 1 signaling occurs exclusively via the type I receptor.

Cited by 540 publications

References 42 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

Extended haplotypes and linkage disequilibrium in the IL1R1–IL1A–IL1B–IL1RN gene cluster: association with knee osteoarthritis

Characterization of new polymorphisms in the 5′UTR of the human interleukin-1 receptor type 1 (IL1R1) gene: linkage to type 1 diabetes and correlation to IL-1RI plasma level

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