ArticlePloS one2013
TNF stimulates nuclear export and secretion of IL-15 by acting on CRM1 and ARF6.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 18 citations in OpenAlex.
- Comparative Evaluation of Synthetic Cytokines for Enhancing Production and Performance of NK92 Cell-Based Therapies.GEN biotechnology · 2023Article
- IL-15/IL-15Rα in SJS/TEN: Relevant Expression ofBiomedicines · 2022Article
- Systemic Interleukins' Profile in Early and Advanced Colorectal Cancer.International journal of molecular sciences · 2021Review
- Brefeldin A and kifunensine modulate LPS-induced lung endothelial hyperpermeability in human and bovine cells.American journal of physiology. Cell physiology · 2021Article
- Complement-activated interferon-γ-primed human endothelium transpresents interleukin-15 to CD8+ T cells.The Journal of clinical investigation · 2020Article
- Cytokine changes associated with the maternal immune activation (MIA) model of autism: A penalized regression approach.PloS one · 2020Article
- Brefeldin A reduces tumor necrosis factor-α-stimulated production of inflammatory mediators by suppressing the Akt, mTOR, and NF-κB pathways in human keratinocytes.Naunyn-Schmiedeberg's archives of pharmacology · 2016Article
- David and Goliath: chemical perturbation of eukaryotes by bacteria.Journal of industrial microbiology & biotechnology · 2016Review
- F-BOX proteins in cancer cachexia and muscle wasting: Emerging regulators and therapeutic opportunities.Seminars in cancer biology · 2016Review
- TLR-9 and IL-15 Synergy Promotes the In Vitro Clonal Expansion of Chronic Lymphocytic Leukemia B Cells.Journal of immunology (Baltimore, Md. : 1950) · 2015Article
- Cytokine Secretion in Macrophages: SNAREs, Rabs, and Membrane Trafficking.Frontiers in immunology · 2014Review
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Interleukin (IL)-15 is a ubiquitously expressed cytokine that in the basal state is mainly localized intracellularly, including the nucleus. Unexpectedly, tumor necrosis factor-α (TNF) time-dependently induced nuclear export of IL-15Rα and IL15. This process was inhibited by leptomycine B (LMB), a specific inhibitor of nuclear export receptor chromosomal region maintenance 1 (CRM1). In the presence of TNF, LMB co-treatment led to accumulation of both IL-15Rα and IL-15 in the nucleus of HeLa cells, suggesting that CRM1 facilitates nuclear export and that TNF enhances CRM1 activity. Once in the cytoplasm, IL-15 showed partial co-localization with late endosomes but very little with other organelles tested 4 h after TNF treatment. IL-15Rα showed co-localization with both early and late endosomes, and to a lesser extent with endoplasmic reticulum and Golgi. This indicates different kinetics and possibly different trafficking routes of IL-15 from its specific receptor. The TNF-induced secretion of IL-15 was attenuated by pretreatment of cells by brefeldin A that inhibits ER-to-Golgi transport, or by use of domain negative ADP-ribosylation factor 6 (ARF6) that interferes with exocytotic sorting. We conclude that TNF abolishes nuclear localization of IL-15 and IL-15Rα by acting on CRM1, and it facilitates exocytosis of IL-15 with the involvement of ARF6.
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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.