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• W2113313120 abstract "Lung inflammation can result from exposure to multiple types of inflammatory stimuli. Fibroblasts, key structural cells in the lung that are integral to inflammation and wound healing, produce inflammatory mediators after exposure to stimuli such as IL-1β. We and others have shown that the NF-κB member RelB has anti-inflammatory properties in mice. Little is known, however, about the anti-inflammatory role of RelB in human cells and how it functions. MicroRNAs (miRNAs), a novel class of small, noncoding RNAs, can mediate inflammatory signaling pathways, including NF-κB, through regulation of target gene expression. Our goal was to analyze the anti-inflammatory properties of RelB in human lung fibroblasts. We hypothesized that RelB regulates inflammatory mediator production in lung fibroblasts in part through a mechanism involving miRNAs. To accomplish this, we transfected human lung fibroblasts with a plasmid encoding RelB and small interfering (si)RNA targeting RelB mRNA to overexpress and downregulate RelB, respectively. IL-1β, a powerful proinflammatory stimulus, was used to induce NF-κB-driven inflammatory responses. RelB overexpression reduced IL-1β-induced cyclooxygenase (Cox)-2, PGE₂, and cytokine production, and RelB downregulation increased Cox-2 expression and PGE₂ production. Furthermore, RelB overexpression increased IL-1β-induced expression of miRNA-146a, an NF-κB-dependent miRNA with anti-inflammatory properties, whereas RelB downregulation reduced miRNA-146a. miR-146a overexpression ablated the effects of RelB downregulation on IL-1β-induced Cox-2, PGE₂, and IL-6 production, suggesting that RelB mediates IL-1β-induced inflammatory mediator production in lung fibroblasts through miRNA-146a. RelB and miRNA-146a may therefore be new therapeutic targets in the treatment of lung inflammation caused by various agents and conditions." @default.
• W2113313120 created "2016-06-24" @default.
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• W2113313120 date "2013-06-01" @default.
• W2113313120 modified "2023-09-26" @default.
• W2113313120 title "Attenuation of inflammatory mediator production by the NF-κB member RelB is mediated by microRNA-146a in lung fibroblasts" @default.
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• W2113313120 doi "https://doi.org/10.1152/ajplung.00352.2012" @default.
• W2113313120 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/3680764" @default.
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