Ginsenoside Rb1 alleviates lipopolysaccharide-induced inflammatory injury by downregulating miR-222 in WI-38 cells

2020 ◽  
Author(s):  
Erhu Wei ◽  
Xiao Fang ◽  
Peisheng Jia ◽  
Mingxia Li ◽  
Peina Jin ◽  
...  
Keyword(s):  
Cell Viability ◽  
Inflammatory Cytokine ◽  
Molecular Mechanisms ◽  
Cytokine Production ◽  
Panax Notoginseng ◽  
Lung Fibroblasts ◽  
Ginsenoside Rb1 ◽  
Inflammatory Cytokine Production ◽  
Inflammatory Injury ◽  
Factor Α

Abstract Background Pneumonia is a serious respiratory tract infection disease in children, which threatens to the health or life of children patients. Ginsenoside Rb1 (Rb1) is a principle active ingredient extracted from the root of Panax notoginseng (Burk.) F.H.Chen with anti-inflammatory effect. Our study aimed to determine the effects and molecular mechanisms of Rb1 on lipopolysaccharide (LPS)-induced inflammatory injury of lung fibroblasts WI-38 cells. Methods Cell viability and apoptosis were evaluated by CCK-8 and flow cytometry analysis, respectively. The production of inflammatory cytokines including tumor necrosis factor-α (TNF-α), interleukin (IL)-lβ, and IL-6 were measured by ELISA and RT-qPCR. miR-222 expression was examined by RT-qPCR. The expression levels of the nuclear factor-kappa B (NF-κB) p65 and phosphorylated p65 were detected by western blot. Results LPS stimulation induced WI-38 cell inflammatory injury by inhibiting cell viability, and inducing apoptosis and inflammatory cytokine production, while treatment with Rb1 significantly attenuated LPS-induced inflammatory injury in WI-38 cells. Additionally, Rb1 decreased LPS-induced upregulation of miR-222 and activation of the NF-κB pathway in WI-38 cells. Overexpression of miR-222 abolished the inhibitory effects of Rb1 on LPS-induced viability reduction, apoptosis, inflammatory cytokine production and activation of the NF-κB pathway. Conclusion Rb1 alleviated LPS-induced inflammatory injury in WI-38 cells via downregulating miR-222 and inactivation of the NF-κB pathway, contributing to our understanding of the effects and molecular mechanism of Rb1 in pneumonia.

scholarly journals Ginsenoside Rb1 Alleviates Lipopolysaccharide-Induced Inflammatory Injury by Downregulating miR-222 in WI-38 Cells

2021 ◽  
Vol 30 ◽  
pp. 096368972110027
Author(s):  
Erhu Wei ◽  
Xiao Fang ◽  
Peisheng Jia ◽  
Mingxia Li ◽  
Peina Jin ◽  
...  
Keyword(s):  
Cell Viability ◽  
Inflammatory Cytokine ◽  
Molecular Mechanisms ◽  
Cytokine Production ◽  
Panax Notoginseng ◽  
Lung Fibroblasts ◽  
Ginsenoside Rb1 ◽  
Inflammatory Cytokine Production ◽  
Inflammatory Injury ◽  
Infection Disease

Pneumonia is a serious respiratory tract infection disease in children, which threatens to the health or life of children patients. Ginsenoside Rb1 (Rb1) is a principle active ingredient extracted from the root of Panax notoginseng (Burk.) F.H. Chen with anti-inflammatory effect. Our study aimed to determine the effects and molecular mechanisms of Rb1 on lipopolysaccharide (LPS)-induced inflammatory injury of lung fibroblasts WI-38 cells. Cell viability and apoptosis were evaluated by CCK-8 and flow cytometry, respectively. The production of inflammatory cytokines were measured by ELISA and RT-qPCR. miR-222 expression was examined by RT-qPCR. The expression levels of the nuclear factor-kappa B (NF-κB) p65 and phosphorylated p65 were detected by western blot. We found that LPS stimulation induced WI-38 cell inflammatory injury by inhibiting cell viability, and inducing apoptosis and inflammatory cytokine production, while treatment with Rb1 significantly attenuated LPS-induced inflammatory injury in WI-38 cells. Additionally, Rb1 decreased LPS-induced upregulation of miR-222 and activation of the NF-κB pathway in WI-38 cells. Overexpression of miR-222 abolished the inhibitory effects of Rb1 on LPS-induced viability reduction, apoptosis, inflammatory cytokine production and activation of the NF-κB pathway. In conclusion, Rb1 alleviated LPS-induced inflammatory injury in WI-38 cells via downregulating miR-222 and inactivation of the NF-kB pathway.

scholarly journals Trimetazidine protects retinal ganglion cells from acute glaucoma via the Nrf2/Ho-1 pathway

2017 ◽  
Vol 131 (18) ◽  
pp. 2363-2375 ◽  
Author(s):  
Peixing Wan ◽  
Wenru Su ◽  
Yingying Zhang ◽  
Zhidong Li ◽  
Caibin Deng ◽  
...  
Keyword(s):  
Inflammatory Cytokine ◽  
Molecular Mechanisms ◽  
Cytokine Production ◽  
Therapeutic Potential ◽  
Heme Oxygenase 1 ◽  
Related Factor ◽  
Retinal Ganglion ◽  
Inflammatory Cytokine Production ◽  
Acute Glaucoma

Acute glaucoma is one of the leading causes of irreversible vision impairment characterized by the rapid elevation of intraocular pressure (IOP) and consequent retinal ganglion cell (RGC) death. Oxidative stress and neuroinflammation have been considered critical for the pathogenesis of RGC death in acute glaucoma. Trimetazidine (TMZ), an anti-ischemic drug, possesses antioxidative and anti-inflammatory properties, contributing to its therapeutic potential in tissue damage. However, the role of TMZ in acute glaucoma and the underlying molecular mechanisms remain elusive. Here, we report that treatment with TMZ significantly attenuated retinal damage and RGC death in mice with acute glaucoma, with a significant decrease in reactive oxygen species (ROS) and inflammatory cytokine production in the retina. Furthermore, TMZ treatment directly decreased ROS production and rebalanced the intracellular redox state, thus contributing to the survival of RGCs in vitro. TMZ treatment also reduced the production of inflammatory cytokines in vitro. Mechanistically, the TMZ-mediated inhibition of apoptosis and inflammatory cytokine production in RGCs occurred via the regulation of the nuclear factor erythroid 2-related factor 2/heme oxygenase 1/caspase-8 pathway. Moreover, the TMZ-mediated neuroprotection in acute glaucoma was abrogated when an HO-1 inhibitor, SnPP, was used. Our findings identify potential mechanisms of RGC apoptosis and propose a novel therapeutic agent, TMZ, which exerts a precise neuroprotective effect against acute glaucoma.

scholarly journals A Novel Compound C12 Inhibits Inflammatory Cytokine Production and Protects from Inflammatory Injury In Vivo

PLoS ONE ◽  
2011 ◽  
Vol 6 (9) ◽  
pp. e24377 ◽  
Author(s):  
Yi Wang ◽  
Congcong Yu ◽  
Yong Pan ◽  
Jianling Li ◽  
Yali Zhang ◽  
...  
Keyword(s):  
Inflammatory Cytokine ◽  
Cytokine Production ◽  
Inflammatory Cytokine Production ◽  
Inflammatory Injury

scholarly journals Histone deacetylase inhibitors suppress rheumatoid arthritis fibroblast-like synoviocyte and macrophage IL-6 production by accelerating mRNA decay

2011 ◽  
Vol 71 (3) ◽  
pp. 424-431 ◽  
Author(s):  
Aleksander M Grabiec ◽  
Olexandr Korchynskyi ◽  
Paul P Tak ◽  
Kris A Reedquist
Keyword(s):  
Rheumatoid Arthritis ◽  
Histone Deacetylase ◽  
Inflammatory Cytokine ◽  
Mrna Decay ◽  
Histone Deacetylase Inhibitors ◽  
Molecular Mechanisms ◽  
Cytokine Production ◽  
Trichostatin A ◽  
Binding Activity ◽  
Inflammatory Cytokine Production

BackgroundHistone deacetylase inhibitors (HDACi) display potent therapeutic efficacy in animal models of arthritis and suppress inflammatory cytokine production in rheumatoid arthritis (RA) synovial macrophages and tissue.ObjectivesTo determine the molecular mechanisms contributing to the suppressive effects of HDACi on RA synovial cell activation, using interleukin 6 (IL-6) regulation as a model.MethodsRA fibroblast-like synoviocytes (FLS) and healthy donor macrophages were treated with IL-1β, tumour necrosis factor (TNF)α, lipopolysaccharide or polyinosinic:polycytidylic acid (poly(I:C)) in the absence or presence of the HDACi trichostatin A (TSA) or ITF2357 (givinostat). IL-6 production and mRNA expression was measured by ELISA and quantitative PCR (qPCR), respectively. Protein acetylation and the activation of intracellular signalling pathways were assessed by immunoblotting. The DNA-binding activity of nuclear factor κB (NFκB) and activator protein 1 (AP-1) components was measured by ELISA-based assays.ResultsHDACi (0.25–1.0 μM) suppressed RA FLS IL-6 production induced by IL-1β, TNFα and Toll-like receptor ligands. Phosphorylation of mitogen-activated protein kinases and inhibitor of κBα (IκBα) following IL-1β stimulation were unaffected by HDACi, as were AP-1 composition and binding activity, and c-Jun induction. TSA induced a significant reduction in nuclear retention of NFκB in FLS 24 h after IL-1β stimulation, but this did not reduce NFκB transcriptional activity or correlate temporally with reductions in IL-6 mRNA accumulation. HDACi significantly reduced the stability of IL-6 mRNA in FLS and macrophages.ConclusionsOur study identifies a novel, shared molecular mechanism by which HDACi can disrupt inflammatory cytokine production in RA synovial cells, namely the promotion of mRNA decay, and suggests that targeting HDAC activity may be clinically useful in suppressing inflammation in RA.

scholarly journals Runx1 negatively regulates inflammatory cytokine production by neutrophils in response to Toll-like receptor signaling

2020 ◽  
Vol 4 (6) ◽  
pp. 1145-1158 ◽  
Author(s):  
Dana C. Bellissimo ◽  
Chia-hui Chen ◽  
Qin Zhu ◽  
Sumedha Bagga ◽  
Chung-Tsai Lee ◽  
...  
Keyword(s):  
Inflammatory Cytokine ◽  
Cytokine Production ◽  
Lung Parenchyma ◽  
Nuclear Factor Κb ◽  
Lung Epithelial Cells ◽  
Toll Like Receptor ◽  
Tlr4 Signaling ◽  
Inflammatory Cytokine Production ◽  
Proinflammatory Mediators ◽  
Factor Α

Abstract RUNX1 is frequently mutated in myeloid and lymphoid malignancies. It has been shown to negatively regulate Toll-like receptor 4 (TLR4) signaling through nuclear factor κB (NF-κB) in lung epithelial cells. Here we show that RUNX1 regulates TLR1/2 and TLR4 signaling and inflammatory cytokine production by neutrophils. Hematopoietic-specific RUNX1 loss increased the production of proinflammatory mediators, including tumor necrosis factor-α (TNF-α), by bone marrow neutrophils in response to TLR1/2 and TLR4 agonists. Hematopoietic RUNX1 loss also resulted in profound damage to the lung parenchyma following inhalation of the TLR4 ligand lipopolysaccharide (LPS). However, neutrophils with neutrophil-specific RUNX1 loss lacked the inflammatory phenotype caused by pan-hematopoietic RUNX1 loss, indicating that dysregulated TLR4 signaling is not due to loss of RUNX1 in neutrophils per se. Rather, single-cell RNA sequencing indicates the dysregulation originates in a neutrophil precursor. Enhanced inflammatory cytokine production by neutrophils following pan-hematopoietic RUNX1 loss correlated with increased degradation of the inhibitor of NF-κB signaling, and RUNX1-deficient neutrophils displayed broad transcriptional upregulation of many of the core components of the TLR4 signaling pathway. Hence, early, pan-hematopoietic RUNX1 loss de-represses an innate immune signaling transcriptional program that is maintained in terminally differentiated neutrophils, resulting in their hyperinflammatory state. We hypothesize that inflammatory cytokine production by neutrophils may contribute to leukemia associated with inherited RUNX1 mutations.

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