ArticleThe Journal of biological chemistry2014
A genome-wide small interfering RNA (siRNA) screen reveals nuclear factor-κB (NF-κB)-independent regulators of NOD2-induced interleukin-8 (IL-8) secretion.
Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers, 1 of them a synthesis that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
24 citing papers in PubMed, 1 synthesis or guideline pooled it, 44 citations in OpenAlex.
- Integrative Genome-Wide Association Studies of eQTL and GWAS Data for Gout Disease Susceptibility.Scientific reports · 2019Pooled it
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- Role of necroptosis in traumatic brain and spinal cord injuries.Journal of advanced research · 2022Review
- Massive Loss of Transcription Factors Promotes the Initial Diversification of Placental Mammals.International journal of molecular sciences · 2022Article
- Ubiquitin-specific proteases in inflammatory bowel disease-related signalling pathway regulation.Cell death & disease · 2022Review
- Detection of Neanderthal Adaptively Introgressed Genetic Variants That Modulate Reporter Gene Expression in Human Immune Cells.Molecular biology and evolution · 2022Article
- ARHGEF26 enhances Salmonella invasion and inflammation in cells and mice.PLoS pathogens · 2021Article
- Intestinal mucosa-derived DNA methylation signatures in the penetrating intestinal mucosal lesions of Crohn's disease.Scientific reports · 2021Article
- Aberrant Autophagy Impacts Growth and Multicellular Development in aFrontiers in cell and developmental biology · 2021Article
- MasterPATH: network analysis of functional genomics screening data.BMC genomics · 2020Article
- Impact of different Streptococcus pneumoniae on the secretion of interleukin and adhesin from THP-1 monocytes.Journal of clinical laboratory analysis · 2019Article
- Review
- Long Noncoding RNACells · 2019Review
- Modulation of the NOD-like receptors NOD1 and NOD2: A chemist's perspective.Bioorganic & medicinal chemistry letters · 2019Review
- Identification of regulatory variants associated with genetic susceptibility to meningococcal disease.Scientific reports · 2019Article
- Genome-wide analysis identifies rare copy number variations associated with inflammatory bowel disease.PloS one · 2019Article
- NOD Signaling and Cell Death.Frontiers in cell and developmental biology · 2019Review
- Arsenic and/or copper caused inflammatory response via activation of inducible nitric oxide synthase pathway and triggered heat shock protein responses in testis tissues of chicken.Environmental science and pollution research international · 2018Article
- Integrative Transcriptomic and microRNAomic Profiling Reveals Immune Mechanism for the Resilience to Soybean Meal Stress in Fish Gut and Liver.Frontiers in physiology · 2018Article
- IL-8 and IP-10 expression from human bronchial epithelial cells BEAS-2B are promoted by Streptococcus pneumoniae endopeptidase O (PepO).BMC microbiology · 2017Article
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 1 country.
Funding
Abstract
NOD2 encodes an intracellular multidomain pattern recognition receptor that is the strongest known genetic risk factor in the pathogenesis of Crohn disease (CD), a chronic relapsing inflammatory disorder of the intestinal tract. NOD2 functions as a sensor for bacterial cell wall components and activates proinflammatory and antimicrobial signaling pathways. Here, using a genome-wide small interfering RNA (siRNA) screen, we identify numerous genes that regulate secretion of the proinflammatory cytokine IL-8 in response to NOD2 activation. Moreover, many of the identified IL-8 regulators are linked by protein-protein interactions, revealing subnetworks of highly connected IL-8 regulators implicated in processes such as vesicle formation, mRNA stability, and protein ubiquitination and trafficking. A TNFα counterscreen to induce IL-8 secretion in an NOD2-independent manner reveals that the majority of the identified regulators affect IL-8 secretion irrespective of the initiating stimuli. Using immortalized macrophages, we validate the ubiquitin protease, USP8, and the endosomal sorting protein, VPS28, as negative regulators of NOD2-induced cytokine secretion. Interestingly, several genes that affect NOD2-induced IL-8 secretion are present in loci associated with CD risk by genome-wide association studies, supporting a role for the NOD2/IL-8 pathway, and not just NOD2, in the pathogenesis of CD. Overall, this screen provides a valuable resource in the advancement of our understanding of the genes that regulate the secretion of IL-8.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.