ArticleNucleic acids research2009
Activation of interferon regulatory factor-3 via toll-like receptor 3 and immunomodulatory functions detected in A549 lung epithelial cells exposed to misplaced U1-snRNA.
Article in Nucleic acids research, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 31 citations in OpenAlex.
- Mechanisms of rapid induction of interleukin-22 in activated T cells and its modulation by cyclosporin a.The Journal of biological chemistry · 2012Trial
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- Efferocytosis by macrophages in physiological and pathological conditions: regulatory pathways and molecular mechanisms.Frontiers in immunology · 2024Review
- Implications of m6A-associated snRNAs in the prognosis and immunotherapeutic responses of hepatocellular carcinoma.Frontiers in immunology · 2022Article
- Comprehensive analysis of molecular mechanism and a novel prognostic signature based on small nuclear RNA biomarkers in gastric cancer patients.Open medicine (Warsaw, Poland) · 2022Article
- Impact of mRNA chemistry and manufacturing process on innate immune activation.Science advances · 2020Article
- Identification of U11snRNA as an endogenous agonist of TLR7-mediated immune pathogenesis.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- Apoptotic endothelial cells release small extracellular vesicles loaded with immunostimulatory viral-like RNAs.Scientific reports · 2019Article
- DUSP10 Negatively Regulates the Inflammatory Response to Rhinovirus through Interleukin-1β Signaling.Journal of virology · 2019Article
- Fascin1 suppresses RIG-I-like receptor signaling and interferon-β production by associating with IκB kinase ϵ (IKKϵ) in colon cancer.The Journal of biological chemistry · 2018Article
- CD13 restricts TLR4 endocytic signal transduction in inflammation.Journal of immunology (Baltimore, Md. : 1950) · 2015Article
- MUC18 Differentially Regulates Pro-Inflammatory and Anti-Viral Responses in Human Airway Epithelial Cells.Journal of clinical & cellular immunology · 2014Article
- Article
- Activation of autoreactive B cells by endogenous TLR7 and TLR3 RNA ligands.The Journal of biological chemistry · 2012Article
- Mucins and toll-like receptors: kith and kin in infection and cancer.Cancer letters · 2012Review
- Scavenger receptors in human airway epithelial cells: role in response to double-stranded RNA.PloS one · 2012Article
- Article
- Co-ordinated role of TLR3, RIG-I and MDA5 in the innate response to rhinovirus in bronchial epithelium.PLoS pathogens · 2010Article
- Simian immunodeficiency virus infection alters chemokine networks in lung tissues of cynomolgus macaques: association with Pneumocystis carinii infection.The American journal of pathology · 2010Article
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
U1-snRNA is an integral part of the U1 ribonucleoprotein pivotal for pre-mRNA splicing. Toll-like receptor (TLR) signaling has recently been associated with immunoregulatory capacities of U1-snRNA. Using lung A549 epithelial/carcinoma cells, we report for the first time on interferon regulatory factor (IRF)-3 activation initiated by endosomally delivered U1-snRNA. This was associated with expression of the IRF3-inducible genes interferon-beta (IFN-beta), CXCL10/IP-10 and indoleamine 2,3-dioxygenase. Mutational analysis of the U1-snRNA-activated IFN-beta promoter confirmed the crucial role of the PRDIII element, previously proven pivotal for promoter activation by IRF3. Notably, expression of these parameters was suppressed by bafilomycin A(1), an inhibitor of endosomal acidification, implicating endosomal TLR activation. Since resiquimod, an agonist of TLR7/8, failed to stimulate A549 cells, data suggest TLR3 to be of prime relevance for cellular activation. To assess the overall regulatory potential of U1-snRNA-activated epithelial cells on cytokine production, co-cultivation with peripheral blood mononuclear cells (PBMC) was performed. Interestingly, A549 cells activated by U1-snRNA reinforced phytohemagglutinin-induced interleukin-10 release by PBMC but suppressed that of tumor necrosis factor-alpha, indicating an anti-inflammatory potential of U1-snRNA. Since U1-snRNA is enriched in apoptotic bodies and epithelial cells are capable of performing efferocytosis, the present data in particular connect to immunobiological aspects of apoptosis at host/environment interfaces.
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