ArticlePloS one2013
Altered regulation of ELAVL1/HuR in HLA-B27-expressing U937 monocytic cells.
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 5 papers.
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Who cites it
5 citing papers in PubMed, 8 citations in OpenAlex.
- ELAVL1 primarily couples mRNA stability with the 3' UTRs of interferon-stimulated genes.Cell reports · 2021Article
- Angustoline Inhibited Esophageal Tumors Through Regulating LKB1/AMPK/ELAVL1/LPACT2 Pathway and Phospholipid Remodeling.Frontiers in oncology · 2020Article
- The RNA-Binding Protein HuR in Digestive System Tumors.BioMed research international · 2020Review
- HLA-B27 Correlates with the Intracellular Elimination, Replication, and Trafficking of Salmonella Enteritidis Collected from Reactive Arthritis Patients.Medical science monitor : international medical journal of experimental and clinical research · 2017Article
- MicroRNA-519 enhances HL60 human acute myeloid leukemia cell line proliferation by reducing the expression level of RNA-binding protein human antigen R.Molecular medicine reports · 2015Article
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectiveTo investigate the role of HLA-B27 expression in the regulation of RNA binding protein (RBP) Embryonic Lethal Abnormal Vision (ELAV) L1/Human antigen R (HuR) expression in Salmonella-infected or LPS-stimulated human monocytic cells, since HuR is a critical regulator of the post-transcriptional fate of many genes (e.g. TNFα) important in inflammatory response.
methodsU937 monocytic cells were stably transfected with pSV2neo resistant vector (mock), wild type HLA-B27, or mutated HLA-B27 with amino acid substitutions in the B pocket. Cells were differentiated, infected with Salmonella enteritidis or stimulated with lipopolysaccharide. The expression levels of HuR protein and cleavage products (CP1 and CP2) were detected by Western blotting and flow cytometry. Specific inhibitors were used to study the role of PKR and p38 in HuR expression and generation of CPs. TNFα and IL-10 secretion after p38 and PKR inhibition were measured by ELISA.
resultsFull length HuR is overexpressed and HuR cleavage is disturbed in U937 monocytic cells expressing HLA-B27 heavy chains (HC). Increased full length HuR expression, disturbed cleavage and reduced dependence on PKR after infection correlate with the expression of glutamic acid 45 in the B pocket that is linked to the misfolding of HLA-B27.
conclusionResults show that the expression of HLA-B27 HCs modulates the intracellular environment of U937 monocyte/macrophages by altering HuR regulation. This phenomenon is at least partly dependent on the misfolding feature of the B27 molecule. Since HuR is an important regulator of multiple genes involved in inflammatory response observations offer an explanation how HLA-B27 may modulate inflammatory response.
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