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Interleukin 1 Receptor Accessory Protein

Caterina Montani, Laura Gritti, Stefania Beretta, Chiara Verpelli, Carlo Sala
Since the first observation that described a patient with a mutation in IL1RAPL1 gene associated with intellectual disability in 1999, the function of IL1RAPL1 have been extensively studied by a number of laboratories. In this review, we summarize all the major data describing the synaptic and neuronal functions of IL1RAPL1 and recapitulate most of the genetic deletion identified in humans and associated to intellectual disability (ID) and autism spectrum disorders (ASD). All the data clearly demonstrate that IL1RAPL1 is a synaptic adhesion molecule localized at the postsynaptic membrane...
December 11, 2018: Developmental Neurobiology
Jie Meng, Yan Zou, Jifei Chen, Fengxian Qin, Xiang Chen, Xiaoli Chen, Shengming Dai
Activation of Toll-like receptor 4 (TLR4) and its accessory proteins myeloid differentiation protein 2 (MD-2) can trigger immune and inflammatory activities, and contribute to developing chronic inflammatory diseases. The formation of the TLR4/MD-2 complex after binding to lipopolysaccharide (LPS) leads to the activation of downstream signaling pathway. The present study was designed to reveal the effect of the soluble form of the extracellular TLR4 domain and MD-2 (sTLR4/sMD-2) complex lacking the intracellular and transmembrane domains on various aspects of LPS-induced inflammation in vivo and in vitro ...
December 2018: Experimental and Therapeutic Medicine
Liya Li, Honglin Zhu, Xiaoxia Zuo
Interleukin-33 (IL-33), a member of the IL-1 superfamily, functions as a traditional cytokine and nuclear factor. It is proposed to have an "alarmin" role. IL-33 mediates biological effects by interacting with the ST2 receptor and IL-1 receptor accessory protein, particularly in innate immune cells and T helper 2 cells. Recent articles have described IL-33 as an emerging pro-fibrotic cytokine in the immune system as well as a novel potential target for systemic sclerosis. Here, we review the available information and focus on the pleiotropic expression and pathogenesis of IL-33 in systemic sclerosis, as well as the feasibility of using IL-33 in clinical applications...
2018: Frontiers in Immunology
Jaewoo Hong, Soohyun Kim, P Charles Lin
Interleukin-33 (IL-33) is one of the members of the IL-1 family of cytokines and a ligand of ST2 and IL-1 receptor accessory protein (IL-1RAcP) that is known to affect Th2 inflammatory response with partial effects on Th1 responses. This cytokine is released by epithelial and smooth muscle cells of the airway system during their injury by several environmental stimuli, such as allergens, viruses, helminths, and pollutants. IL-33 is an alarmin that acts as an endogenous danger signal, and it has been known to affect various types of cells, such as mast cells, basophils, eosinophils, T cells, and specific subsets of innate lymphoid cells (ILCs)...
September 25, 2018: Journal of Interferon & Cytokine Research
Matthew R Alexander, Allison E Norlander, Fernando Elijovich, Ravi V Atreya, Amadou Gaye, Juan S Gnecco, Cheryl L Laffer, Cristi L Galindo, Meena S Madhur
BACKGROUND AND PURPOSE: Monocytes play a critical role in hypertension. The purpose of our study was to use an unbiased approach to determine whether hypertensive individuals on conventional therapy exhibit an altered monocyte gene expression profile and to perform validation studies of selected genes to identify novel therapeutic targets for hypertension. EXPERIMENTAL APPROACH: Next generation RNA sequencing identified differentially expressed genes in a small discovery cohort of normotensive and hypertensive individuals...
May 18, 2018: British Journal of Pharmacology
Kelly Mitchell, Laura Barreyro, Tihomira I Todorova, Samuel J Taylor, Iléana Antony-Debré, Swathi-Rao Narayanagari, Luis A Carvajal, Joana Leite, Zubair Piperdi, Gopichand Pendurti, Ioannis Mantzaris, Elisabeth Paietta, Amit Verma, Kira Gritsman, Ulrich Steidl
The surface molecule interleukin-1 receptor accessory protein (IL1RAP) is consistently overexpressed across multiple genetic subtypes of acute myeloid leukemia (AML) and other myeloid malignancies, including at the stem cell level, and is emerging as a novel therapeutic target. However, the cell-intrinsic functions of IL1RAP in AML cells are largely unknown. Here, we show that targeting of IL1RAP via RNA interference, genetic deletion, or antibodies inhibits AML pathogenesis in vitro and in vivo, without perturbing healthy hematopoietic function or viability...
June 4, 2018: Journal of Experimental Medicine
Fei Liu, Miao Dai, Qinyang Xu, Xiaolu Zhu, Yang Zhou, Shuheng Jiang, Yahui Wang, Zhihong Ai, Li Ma, Yanli Zhang, Lipeng Hu, Qin Yang, Jun Li, Shujie Zhao, Zhigang Zhang, Yincheng Teng
High-risk human papillomavirus oncoproteins E6 and E7 are the major etiological factors of cervical cancer but are insufficient for malignant transformation of cervical cancer. Dysregulated alternative splicing, mainly ascribed to aberrant splicing factor levels and activities, contributes to most cancer hallmarks. However, do E6 and E7 regulate the expression of splicing factors? Does alternative splicing acts as an "accomplice" of E6E7 to promote cervical cancer progression? Here, we identified that the splicing factor SRSF10, which promotes tumorigenesis of cervix, was upregulated by E6E7 via E2F1 transcriptional activation...
May 2018: Oncogene
Jun Yin, Changqing Dong, Weifeng Tang, Ruiping Liu, Suocheng Chen, Liang Zheng, Haiyong Gu
The present study was conducted to investigate the association between gastric cardiac adenocarcinoma (GCA) and four functional single-nucleotide polymorphisms (SNPs), including interleukin 18 ( IL18 ) rs360719 A>G, IL18 receptor 1 (IL18R1) rs13015714 G>T, IL18 receptor accessory protein (IL18RAP) rs917997 C>T and interleukin 28B (IL28B) rs8099917 T>G variants. A hospital-based case-control study was performed to evaluate the genetic effects of these SNPs. A total of 243 GCA cases and 476 controls were enrolled in this study...
December 2017: Molecular and Clinical Oncology
Diana Boraschi, Paola Italiani, Sabrina Weil, Michael U Martin
The extracellular forms of the IL-1 cytokines are active through binding to specific receptors on the surface of target cells. IL-1 ligands bind to the extracellular portion of their ligand-binding receptor chain. For signaling to take place, a non-binding accessory chain is recruited into a heterotrimeric complex. The intracellular approximation of the Toll-IL-1-receptor (TIR) domains of the 2 receptor chains is the event that initiates signaling. The family of IL-1 receptors (IL-1R) includes 10 structurally related members, and the distantly related soluble protein IL-18BP that acts as inhibitor of the cytokine IL-18...
January 2018: Immunological Reviews
Martina Molgora, Domenico Supino, Alberto Mantovani, Cecilia Garlanda
Interleukin-1 receptor family members (ILRs) and Toll-Like Receptors (TLRs) are key players in immunity and inflammation and are tightly regulated at different levels. Most cell types, including cells of the innate and adaptive immune system express ILRs and TLRs. In addition, IL-1 family members are emerging as key players in the differentiation and function of innate and adaptive lymphoid cells. IL-1R2 and IL-1R8 (also known as TIR8 or SIGIRR) are members of the ILR family acting as negative regulators of the IL-1 system...
January 2018: Immunological Reviews
Xiaomin Zhao, Xiaoyuan Bai, Lijuan Guan, Juejun Li, Xiangjun Song, Xuelian Ma, Jianxiong Guo, Zhichao Zhang, Qian Du, Yong Huang, Dewen Tong
Transmissible gastroenteritis virus (TGEV), a member of the coronaviridae family, could cause fatal diarrhea of piglets and result in numerous economic losses. Previous studies demonstrated that TGEV infection could lead to mitochondrial damage and upregulate miR-4331 level. So miR-4331 may play an important regulatory role in the control of mitochondrial function. To explore the potential role of miR-4331 in mitochondrial damage, we adopted a strategy consisting of quantitative proteomic analysis of porcine kidney (PK-15) cells in response to miR-4331 and TGEV infection...
February 2018: Molecular & Cellular Proteomics: MCP
Li Zhou, Viktor Todorovic, Steve Kakavas, Bernhard Sielaff, Limary Medina, Leyu Wang, Ramkrishna Sadhukhan, Henning Stockmann, Paul L Richardson, Enrico DiGiammarino, Chaohong Sun, Victoria Scott
IL-36 cytokines signal through the IL-36 receptor (IL-36R) and a shared subunit, IL-1RAcP (IL-1 receptor accessory protein). The activation mechanism for the IL-36 pathway is proposed to be similar to that of IL-1 in that an IL-36R agonist (IL-36α, IL-36β, or IL-36γ) forms a binary complex with IL-36R, which then recruits IL-1RAcP. Recent studies have shown that IL-36R interacts with IL-1RAcP even in the absence of an agonist. To elucidate the IL-36 activation mechanism, we considered all possible binding events for IL-36 ligands/receptors and examined these events in direct binding assays...
January 12, 2018: Journal of Biological Chemistry
Li-Xia Du, Yan-Qing Wang, Guo-Qiang Hua, Wen-Li Mi
Interleukin (IL)-33 is a member of the interleukin-1 cytokine family that is produced by many different types of tissues including the central nervous system (CNS). IL-33 mediates its effects via its heterodimeric receptor complex, comprised of ST2 and the IL-1 receptor accessory protein (IL-1RAcp). As a pleiotropic nuclear cytokine, IL-33 is a crucial factor in the development of cardiovascular diseases, allergic diseases, infectious diseases, and autoimmune diseases. Recently, accumulated evidence shows that the IL-33/ST2 axis plays a crucial and diverse role in the pathogenesis of CNS diseases, including neurodegenerative diseases, cerebrovascular diseases, infectious diseases, traumatic CNS injury, chronic pain, etc...
January 15, 2018: Neuroscience
Tomoyuki Nishizaki
Interleukin-33 (IL-33) is recognized to transmit a signal through a heterodimeric receptor complex ST2/interleukin-1 receptor accessory protein (IL-1RAcP) bearing activation of myeloid differentiation factor 88 (MyD88). High-frequency stimulation to the Schaffer collateral induced long-term potentiation (LTP) in the CA1 region of hippocampal slices from wild-type control mice. Schaffer collateral/CA1 LTP in IL-33-deficient mice was significantly suppressed, which was neutralized by application with IL-33. Similar suppression of the LTP was found with MyD88-deficient mice but not with ST2-deficient mice...
2017: Neural Plasticity
Seoung Youn Won, Cha Yeon Kim, Doyoun Kim, Jaewon Ko, Ji Won Um, Sung Bae Lee, Matthias Buck, Eunjoon Kim, Won Do Heo, Jie-Oh Lee, Ho Min Kim
The leukocyte common antigen-related receptor protein tyrosine phosphatases (LAR-RPTPs) are cellular receptors of heparan sulfate (HS) and chondroitin sulfate (CS) proteoglycans that direct axonal growth and neuronal regeneration. LAR-RPTPs are also synaptic adhesion molecules that form trans -synaptic adhesion complexes by binding to various postsynaptic adhesion ligands, such as Slit- and Trk-like family of proteins (Slitrks), IL-1 receptor accessory protein-like 1 (IL1RAPL1), interleukin-1 receptor accessory protein (IL-1RAcP) and neurotrophin receptor tyrosine kinase C (TrkC), to regulate synaptogenesis...
2017: Frontiers in Molecular Neuroscience
Sebastian Günther, Daniel Deredge, Amanda L Bowers, Alessandra Luchini, Daniel A Bonsor, Robert Beadenkopf, Lance Liotta, Patrick L Wintrode, Eric J Sundberg
Within the interleukin 1 (IL-1) cytokine family, IL-1 receptor accessory protein (IL-1RAcP) is the co-receptor for eight receptor-cytokine pairs, including those involving cytokines IL-1β and IL-33. Unlike IL-1β, IL-33 does not have a signaling complex that includes both its cognate receptor, ST2, and the shared co-receptor IL-1RAcP, which we now present here. Although the IL-1β and IL-33 complexes shared structural features and engaged identical molecular surfaces of IL-1RAcP, these cytokines had starkly different strategies for co-receptor engagement and signal activation...
September 19, 2017: Immunity
Verena Schmitt, Madelaine Hahn, Verena Kästele, Olga Wagner, Maximilian Wiendl, Anja Derer, Adriano Taddeo, Stefanie Hahne, Andreas Radbruch, Hans-Martin Jäck, Wolfgang Schuh, Dirk Mielenz, Steffen Gay, Georg Schett, Axel J Hueber, Silke Frey
The IL-1 family member IL-36α has proinflammatory and pathogenic properties in psoriasis. IL-36α binds to the IL-36 receptor leading to nuclear factor kappa B/mitogen activated protein kinase mediated cytokine release. The IL-36R antagonist prevents recruitment of IL-1 receptor accessory protein and therefore IL-36-dependent cell activation. In inflamed human tissue, we previously could show that resident B cells and plasma cells (PC) express IL-36α. Further, fibroblast-like synoviocytes (FLS) produced proinflammatory cytokines upon IL-36α-stimulation...
December 2017: European Journal of Immunology
Niranjala Gajanayaka, Shifawn O'Hara, Yulia Konarski, Jason Fernandes, Kar Muthumani, Maya Kozlowski, Jonathan B Angel, Ashok Kumar
Monocyte-derived Mϕs (MDMs) from HIV-infected patients and MDM infected in vitro with HIV exhibit a reduced ability to secrete various cytokines, including IL-12. Recently, IL-27, an IL-12 family cytokine, was shown to inhibit HIV replication in Mϕ. Whether HIV infection or HIV accessory protein(s) impact IL-27 production in Mϕs remains unknown. Herein, we show that in vitro HIV infection, as well as intracellular HIV-Tat (Tat) and Tat peptides, inhibit LPS-induced IL-27 production in human MDMs, suggesting impairment of the TLR4 signaling pathway...
September 2017: Journal of Leukocyte Biology
Hongyu Shen, Liangpeng Li, Sujin Yang, Dandan Wang, Siying Zhou, Xiu Chen, Jinhai Tang
Tumor necrosis factor receptor-associated factor 6 (TRAF6) is an endogenous adaptor of innate and adaptive immune responses, and serves a crucial role in tumor necrosis factor receptor and toll‑like/interleukin‑1 receptor signaling. Although studies have demonstrated that TRAF6 has oncogenic activity, its potential contributions to breast cancer in human remains largely uninvestigated. The present study examined the expression levels and function of TRAF6 in breast carcinoma (n=32) and adjacent healthy (n=25) tissue samples...
August 2017: Molecular Medicine Reports
Caterina Montani, Mariana Ramos-Brossier, Luisa Ponzoni, Laura Gritti, Andrzej W Cwetsch, Daniela Braida, Yoann Saillour, Benedetta Terragni, Massimo Mantegazza, Mariaelvina Sala, Chiara Verpelli, Pierre Billuart, Carlo Sala
Mutations and deletions of the interleukin-1 receptor accessory protein like 1 (IL1RAPL1) gene, located on the X chromosome, are associated with intellectual disability (ID) and autism spectrum disorder (ASD). IL1RAPL1 protein is located at the postsynaptic compartment of excitatory synapses and plays a role in synapse formation and stabilization. Here, using primary neuronal cultures and Il1rapl1-KO mice, we characterized the role of IL1RAPL1 in regulating dendrite morphology. In Il1rapl1-KO mice we identified an increased number of dendrite branching points in CA1 and CA2 hippocampal neurons associated to hippocampal cognitive impairment...
July 12, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
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