Disease relevance of IL18RAP

• IL-18Ralpha was detected on the surface of naive, GC, and memory B lymphocytes, and IL-18Rbeta was detected on GC and memory, but not naive, B cells; (c) mantle zone, follicular, marginal zone, Burkitt lymphoma (BL), and B-cell chronic lymphocytic leukemia (B-CLL) cells expressed IL-18 mRNA [1].
• Epitope mapping analysis using two kinds of random peptide-displaying phage libraries and an IL-18 alanine mutant (D98A) demonstrated that the h18-108 scFv binds to the site 3 of IL-18, which is suggested to be an association site with the IL-18 receptor beta [2].
• IL1 receptor accessory protein like, a protein involved in X-linked mental retardation, interacts with Neuronal Calcium Sensor-1 and regulates exocytosis [3].

High impact information on IL18RAP

• CD48 via both the peptide portion and GPI glycan triggers the binding to IL-18Rbeta, and the IL-18.IL-18Ralpha.CD48.IL-18Rbeta complex induces cellular signaling [4].
• However, little is known about how IL-18, IL-18Ralpha, and IL-18Rbeta form a high-affinity complex on the cell surface and transduce the signal [4].
• On the other hand, the acetylation of IL18RAP gene occurred both in TH1 and TH2 cells the similar kinetics and on the same with residues, demonstrating that selective histone acetylation was not universally the case for all TH1-expressed genes [5].
• Although IL-18R alpha mRNA was constitutively expressed by RA fibroblast-like synoviocytes, IL-18R beta could not be detected, either with or without stimulation with IL-1 or IL-12 [6].
• IL-18 receptor beta-induced changes in the presentation of IL-18 binding sites affect ligand binding and signal transduction [7].

Biological context of IL18RAP

• IL-18 signals through a two-chain receptor (IL-18R and accessory protein-like subunit, AcPL), and an inhibitory molecule, IL-18 binding protein (IL-18BP), has recently been characterized [8].
• The IL-18R beta cDNA was cloned from a human T-B lymphoblast cDNA library and COS-1 cells were transiently transfected with the IL-18R beta chain and a luciferase reporter [9].
• This suggests that IL-18R beta-induced conformational changes may occur in IL-18R alpha upon dimerization, leading to changes in the presentation of IL-18 binding sites [7].
• The 4 MRX-patients included 3 male sibs of a family, carrying a mutation in the IL-1 receptor accessory protein-like gene, and one male patient member of the MRX-44 family (linkage with LOD-score of 2.90) [10].

Anatomical context of IL18RAP

• IL-1Rrp and AcPL were seen in all samples but were expressed at greater levels in the mucosa of CD patients [11].
• Here we show that in human NK and T cells IFN-alpha and IL-12 strongly up-regulate mRNA expression of the IL-18R components, accessory protein-like (AcPL) and IL-1R-related protein (IL-1Rrp) [12].
• PC-3 and DU 145, but not the well-differentiated cell line LNCaP, expressed IL-18R alpha (IL-1Rrp) protein and transcripts for IL-18R beta (AcPL) [13].
• COS-1 cells lack expression of the IL-18R beta chain [9].
• We conclude that functional reconstitution of the IL-18R beta chain is essential for IL-12-independent proinflammatory activity of IL-18-induced IL-8 in fibroblasts [9].

Regulatory relationships of IL18RAP

• In NKO cells and PBMC, IL-12 increased steady-state mRNA levels of IL-18R alpha and IL-18R beta; the production of IFN-gamma corresponded to IL-12-induced IL-18R alpha and IL-18R beta chains [9].
• The combination of soluble IL-18Ralpha and IL-18Rbeta chains inhibits IL-18-induced IFN-gamma [14].

Analytical, diagnostic and therapeutic context of IL18RAP

• RT-PCR assays showed elevation of IL-18Ralpha and IL-18Rbeta mRNA levels in CD8+ T cells in aGVHD patients [15].

References