Disease relevance of IL1RAP

• Human Hepatitis B Viral e Antigen Interacts with Cellular Interleukin-1 Receptor Accessory Protein and Triggers Interleukin-1 Response [1].
• To investigate the activation of SMases by IL-1, we used an IL-1 receptor type I (IL-1RI)-positive EL4 thymoma cell line, which is defective in IL-1R accessory protein (IL-1RAcP) expression [2].
• The set of 10 transcripts for distinguishing FRI without vs with adenovirus had functions related to interferon induced genes, IL1 receptor accessory protein, and cell interactions [3].

High impact information on IL1RAP

• We show here that IL-1beta-mediated activation of the protein tyrosine kinase Src depended on a MyD88 interaction with the IL-1RI/IL-1RAcP complex [4].
• Interleukin-1 receptor (IL-1RI) is a master regulator of inflammation and innate immunity . When triggered by IL-1beta, IL-1RI aggregates with IL-1R-associated protein (IL-1RAcP) and forms a membrane proximal signalosome that potently activates downstream signaling cascades [5].
• Antibodies directed against IL-1RAcP and transfection of cytoplasmically deleted IL-1RAcP both blocked activation of the pathway leading to NF-kappaB by the three cytokines [6].
• Proportional expression of the different IL-1RAcP splice variants may be an important determinant of responsiveness to IL-1 [7].
• Signal transduction is initiated at the cell membrane by complex formation between extracellular IL-1 and the transmembrane IL-1R type I (IL-1RI) and IL-1R accessory protein (IL-1RAcP) [8].

Biological context of IL1RAP

• We have cloned the human sIL-1RAcP and established by sequence analysis that the human sIL-1RAcP mRNA arises from alternative splicing of the IL-1RAcP gene (shown here to encompass 12 exons spanning more than 56 kb) [8].
• Expression of alternatively spliced interleukin-1 receptor accessory protein mRNAs is differentially regulated during inflammation and apoptosis [9].
• The human gene encoding the interleukin-1 receptor accessory protein (IL1RAP) maps to chromosome 3q28 by fluorescence in situ hybridization and radiation hybrid mapping [10].
• Interleukin-1 receptor accessory protein is constitutively expressed in human endometrium throughout the menstrual cycle [11].
• These results proved that IL-1RAcP is an indispensible molecule in the IL-1 receptor signal transduction complex, necessary to link events on the plasma membrane level to downstream signaling pathways, allowing IL-1-dependent activation of transcription factors and gene expression [12].

Anatomical context of IL1RAP

• By expression cloning in COS-7 cells, we have isolated a cDNA from mouse 3T3-LI cells encoding this putative auxiliary molecule, which we term the IL-1 receptor accessory protein (IL-1R AcP) [13].
• The physical association of ligated IL-1RII with IL-1RAcP was proven by crosslinking experiments with radio-iodinated IL-1 and subsequent immunoprecipitations in normal human B cells and in EL-4 D6/76 cells transiently cotransfected with IL-1RII and IL-1RAcP, respectively [14].
• IL-1 signaling cascade in liver cells and the involvement of a soluble form of the IL-1 receptor accessory protein [8].
• Constitutive expression of IL-1RI, IL-1RAcP, and IL-1Ra was detected in both immortalized and primary human airway epithelial cells [15].

Associations of IL1RAP with chemical compounds

• The increase of plasma corticosterone induced by rhIL-1beta in wild-type (WT) mice was not observed in IL-1RAcP KO mice [16].

Physical interactions of IL1RAP

• The IL-1R accessory protein (IL-1RAcP) plays a role in IL-1R signaling by forming a complex with IL-1RI bound to the IL-1 ligand [17].

Other interactions of IL1RAP

• Anti-peptide 2, 3, and 4 recognized surface expression of IL-1RAcP on the Th2 D10S cells by FACS and inhibited IL-1-driven proliferation [17].
• We also show that the bioactivity of both IL-1ra K145D and the triple mutant IL-1ra K145D/H54P/QGEESN is dependent on interaction with the newly cloned IL-1 receptor accessory protein [18].
• Immunoprecipitation studies reveal an interaction between the activated STAT-3 and the IL-1 receptor accessory protein indicating an association between the two signaling pathways [19].
• These data suggest that A-SMase activity is strongly linked with the internalization of IL-1RI mediated by IL-1RAcP and that A-SMase and N-SMase are activated by different pathways [2].
• Activation of acid sphingomyelinase by interleukin-1 (IL-1) requires the IL-1 receptor accessory protein [2].

Analytical, diagnostic and therapeutic context of IL1RAP

• Expression of IL-1alpha and beta, IL-1 receptor antagonist (IL-1Ra), IL-1RI and II, IL-1R accessory protein (IL-1RAcP) and IL-1beta converting enzyme (ICE) was studied by immunocytochemistry, immunoblotting, ELISA and RT - PCR [20].

References