LncRNA loc105377478 promotes NPs-Nd2O3-induced inflammation in human bronchial epithelial cells through the ADIPOR1/NF-κB axis.

With the wide application of neodymium oxide nanoparticles (NPs-Nd2O3) in various fields, their health hazards have aroused public concern in recent years. However, data regarding the cytotoxicity of NPs-Nd2O3 is limited. In this study, we investigated the function and mechanism of long-chain non-coding RNAs (lncRNAs) in NPs-Nd2O3-induced airway inflammation. Treatment with NPs-Nd2O3 induced an inflammatory response in human bronchial epithelial cells (16HBE) by upregulating the expression of interleukin-6 (IL-6) and interleukin-8 (IL-8). The levels of LDH and intracellular ROS in the cells treated by various doses of NPs-Nd2O3 also increased significantly. After treatment with 10 µg/ml NPs-Nd2O3, RNA microarray and real-time quantitative polymerase chain reaction (qRT-PCR) showed a significant upregulation of lncRNA loc105377478. Functional experiments suggested lncRNA loc105377478 enhanced the expression of IL-6, IL-8 and ROS in NPs-Nd2O3-treated 16HBE cells, and it was further demonstrated that lncRNA loc105377478 promoted the activation of NF-κB by negatively regulating ADIPOR1 expression. Moreover, the expression of IL-6 and IL-8 in NPs-Nd2O3-treated 16HBE cells was regulated by lncRNA loc105377478, which was mediated by the NF-κB signaling pathway. In conclusion, lncRNA loc105377478 promotes NF-κB activation by negatively regulating ADIPOR1 expression, thereby upregulating the expression of IL-6 and IL-8 in 16HBE cells treated with NPs-Nd2O3.

circ_0000638 inhibits neodymium oxide-induced bronchial epithelial cell inflammation through the miR-498-5p/NF-κB axis.

Inhalation of neodymium oxide, a type of rare earth metal, can induce various respiratory diseases, such as lung tissue inflammation, but the associated mechanisms underlying this induction are still unclear. In this study, we explored the role and mechanisms of circular RNA in neodymium oxide-induced airway inflammation. Our study showed that treating human bronchial epithelial (16HBE) cells with neodymium oxide caused an inflammatory response by upregulating the expression of interleukin-8 (IL-8) and interleukin-1 beta (IL-1ß). Quantitative real-time polymerase chain reaction (qRT-PCR) analyses revealed significant downregulation of circRNA_0000638 in neodymium oxide-treated 16HBE cells. Data from functional analyses further showed that circ_0000638 inhibited inflammation induced by neodymium oxide in 16HBE cells. circ_0000638 targeted miR-498-5p and further increased the expression of NKRF (NF-κB repressing factor), which inhibited the activation of NF-κB (nuclear factor κB). Moreover, circ_0000638 reduced the expression of IL-8 and IL-1ß by inhibiting NF-κB activation in neodymium oxide-treated 16HBE cells. These results suggest that circ_0000638 can inhibit NF-κB activation by competitively binding to miR-498-5p, further downregulating the expression of IL-8 and IL-1ß in neodymium oxide-treated 16HBE cells.

Circular RNA 0039411 Is Involved in Neodymium Oxide-induced Inflammation and Antiproliferation in a Human Bronchial Epithelial Cell Line via Sponging miR-93-5p.

Adverse health effects induced by neodymium oxide (Nd2O3) particles have raised concern as a result of their increasing applications in various arenas. However, information on their potential cytotoxicity is currently limited. In the present study, we investigated the underlying cytotoxicity of Nd2O3 in human bronchial epithelial cells (16HBE) and the potential mechanisms mediated by circular RNAs (circRNAs). Nd2O3 exposure initiated an inflammatory response in 16HBE cells via the release of the proinflammatory cytokines interleukin (IL)-6 and IL-8. The 5-ethynyl-2'-deoxyuridine assays showed that Nd2O3 treatment inhibited 16HBE cell proliferation and caused cell cycle arrest at G0/G1 phase and cell apoptosis. Microarray analyses demonstrated that Nd2O3 treatment altered circRNA expression profiles and significantly upregulated circRNA 0039411 (circ_0039411) in 16HBE cells. Further functional studies showed that silencing circ_0039411 prevented Nd2O3-induced inflammation and reversed its antiproliferative effect by moderating the G0/G1 phase cell cycle arrest, whereas overexpression of circ_0039411 had the opposite effects. Luciferase reporter assays showed that circ_0039411 bound to miR-93-5p, whereas fluorescence in situ hybridization showed that circ_0039411 and miR-93-5p colocalized in the cytoplasm. Moreover, transfection of 16HBE cells with a miR-93-5p mimic decreased the phosphorylation of signal transducer and activator of transcription 3 (STAT3). The levels of phospho-STAT3 were decreased by circ_0039411 silencing and elevated after circ_0039411 overexpression. These results suggested that upregulation of circ_0039411 mediated Nd2O3-induced inflammation and dysfunction by sponging miR-93-5p.

[Gallic acid inhibits inflammatory response of RAW264.7 macrophages by blocking the activation of TLR4/NF-κB induced by LPS].

Objective To observe the influence of gallic acid on Toll-like receptor 4/nuclear factor-κB (TLR4/NF-κB) pathway in the RAW264.7 macrophages stimulated by lipopolysaccharide (LPS). Methods RAW264.7 macrophages were divided into the following groups: control group, LPS group, LPS combined with gallic acid group, LPS combined with pyrrolidine dithiocarbamate (PDTC) group and LPS combined with dexamethasone (DM) group. RAW264.7 cells were cultured for 24 hours after corresponding treatments. The levels of tumor necrosis factor α (TNF-α), interleukin-1 (IL-1) and IL-6 were detected by ELISA. The levels of TLR4 and NF-κB mRNAs were tested by real-time PCR. The levels of p-IκBα, p65, p-p65 and TLR4 proteins were examined by Western blotting. Results The expression levels of TNF-α, IL-1 and IL-6 were up-regulated in the RAW264.7 macrophages after stimulated by LPS. Gallic acid could reduce the elevated expression levels of TNF-α, IL-1 and IL-6 induced by LPS. The expression of TLR4 significantly increased after stimulated by LPS and NF-κB was activated. Gallic acid could reverse the above changes and prevent the activation of NF-κB. Conclusion Gallic acid could inhibit LPS-induced inflammatory response in RAW264.7 macrophages via TLR4/NF-κB pathway.