Pterostilbene and 4′-Methoxyresveratrol Inhibited Lipopolysaccharide-Induced Inflammatory Response in RAW264.7 Macrophages

Yao, Yun; Liu, Kehai; Zhao, Yueliang; Hu, Xiaoqian; Wang, Mingfu

doi:10.3390/molecules23051148

Cited by 28 publications

(20 citation statements)

References 34 publications

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“…Macrophages are a vital component of the immune system, and play a large role in inflammatory processes. As important immune cells, macrophages respond immediately to microbial infection and directly engulf or indirectly eliminate pathogens by releasing multiple inflammatory mediators [5]. Lipopolysaccharide (LPS), a major component of gram-negative bacterial cell walls, is one of the most potent stimulators of innate immunity.…”

Section: Introductionmentioning

confidence: 99%

m6A Reader YTHDF2 Regulates LPS-Induced Inflammatory Response

Feng

et al. 2019

IJMS

155

130

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N6-methyladenosine (m6A) is an abundant mRNA modification that affects multiple biological processes, including those involved in the cell stress response and viral infection. YTH domain family 2 (YTHDF2) is an m6A-binding protein that affects the localization and stability of targeted mRNA. RNA-binding proteins (RBPs) can regulate the stability of inflammatory gene mRNA transcripts, thus participating in the regulation of inflammatory processes. As an RBP, the role of YTHDF2 in the LPS-induced inflammatory reaction has not been reported. To elucidate the function of YTHDF2 in the inflammatory response of macrophages, we first detected the expression level of YTHDF2 in RAW 264.7 cells, and found that it was upregulated after LPS stimulation. YTHDF2 knockdown significantly increased the LPS-induced IL-6, TNF-α, IL-1β, and IL-12 expression and the phosphorylation of p65, p38, and ERK1/2 in NF-κB and MAPK signaling. Moreover, the upregulated expression of TNF-α and IL-6 in cells with silenced YTHDF2 expression was downregulated by the NF-κB, p38, and ERK inhibitors. YTHDF2 depletion increased the expression and stability of MAP2K4 and MAP4K4 mRNAs. All of these results suggest that YTHDF2 knockdown increases mRNA expression levels of MAP2K4 and MAP4K4 via stabilizing the mRNA transcripts, which activate MAPK and NF-κB signaling pathways, which promote the expression of proinflammatory cytokines and aggravate the inflammatory response in LPS-stimulated RAW 264.7 cells.

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Section: Introductionmentioning

confidence: 99%

m6A Reader YTHDF2 Regulates LPS-Induced Inflammatory Response

Feng

et al. 2019

IJMS

155

130

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“…To estimate the cytotoxic effect of HES, cell viability assay was performed in HepG2 cells by MTT assay. When the cell viability is above 80%, the drug can be thought to have no significant cytotoxicity on cell growth (Johan, Gertjan, & Jacqueline, ; Xu et al, ; Yao, Liu, Zhao, Hu, & Wang, ). As shown in Figure , HES‐1 μmol/L,HES‐5 μmol/L, and HES‐25 μmol/L had no significant cytotoxicity in the HepG2 cells after 24 hr of treatment ( p ≥ .05).…”

Section: Resultsmentioning

confidence: 99%

Hesperidin ameliorates insulin resistance by regulating the IRS1‐GLUT2 pathway via TLR4 in HepG2 cells

Tian

Liu

et al. 2019

Phytotherapy Research

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The aim of this study was to evaluate the effect and mechanism of hesperidin (HES) on insulin resistance (IR) in the human hepatocellular carcinoma cell line (HepG2 cells). HepG2 cells were induced with lipopolysaccharide (LPS) as a model of IR and treated with HES at three dosages. Next, the levels of interleukin‐6 (IL‐6) and tumor necrosis factor‐α (TNF‐α), the glucose content, and glucose uptake were evaluated by enzyme‐linked immunosorbent assay, glucose oxidase‐peroxidase method (GOD‐POD), or (2‐(N‐(7‐nitrobenz‐2‐oxa‐1, 3‐diazol‐4‐yl)amino)‐2‐deoxyglucose) (2‐NBDG). Moreover, the protein expression of toll‐like receptors 4 (TLR4), insulin receptor substrate 1 (IRS1), nuclear factor kappa B (NF‐κB), and glucose transporter 2 (GLUT2) in HepG2 cells treated with HES were assessed via western blotting analysis. In addition, GLUT2 protein expression exposed to HES was detected following treatment with TLR4 inhibitor (HTA125). Our results demonstrated that HES decreased the levels of TNF‐α and IL‐6, attenuated the glucose content in culture medium and increased glucose uptake in insulin‐resistant HepG2 cells in vitro. Moreover, HES upregulated the expression of IRS1 and GLUT2 protein and downregulated the protein expression of TLR4 and NF‐κB in insulin‐resistant HepG2 cells. The expression of GLUT2 protein had no significant changes when treated with HES after blockade of TLR4. HES attenuated IR in LPS‐inducedinsulin‐resistant HepG2 cells. Therefore, regulating the IRS1‐GLUT2 pathway via TLR4 represents a potential mechanism of HES on IR in HepG2 cells.

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“…iNOS and COX-2 coordinate with each other, directly damage the DNA and protein of cells, and play an important role in activating NF-κB. At present, many in vivo and in vitro experiments have shown that PTER can play a powerful anti-inflammatory role by inhibiting the NF-κB signaling pathway, which can mediate the regulation of a variety of inflammatory mediators, including COX-2, iNOS, TNF-α, IL-6 and IL-1β and so on ( Cichocki et al, 2008 ; Zhang and Zhang, 2016 ; Yao et al, 2018 ). It was found that p-p65 and p -IκB proteins in lung tissue of ALI mice were significantly higher than those in blank group.…”

Section: Discussionmentioning

confidence: 99%

Protective Effects of Pterostilbene on Lipopolysaccharide-Induced Acute Lung Injury in Mice by Inhibiting NF-κB and Activating Nrf2/HO-1 Signaling Pathways

et al. 2021

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Pterostilbene (PTER) is a kind of stilbene compound with biological activity isolated from plants such as red sandalwood, blueberry and grape. It has anti-tumor, anti-bacterial, anti-oxidation and other pharmacological activities. However, the underlying mechanism of the protective effect of PTER on lipopolysaccharide (LPS)-induced acute lung injury (ALI) remained not clarified. In this study, LPS was used to establish a mouse model of ALI. Bronchoalveolar lavage fluid (BALF) was collected for inflammatory cells, and the wet-to-dry weight ratio of the lungs was measured. The activities of myeloperoxidase (MPO), antioxidant indexes such as superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px) and oxidation index such as malondialdehyde (MDA) in lung tissues of mice were measured by the corresponding kits. The levels of Cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), TNF-α, IL-6 and IL-1β in lung tissues of mice were detected by quantitative real-time polymerase chain reaction (qRT-PCR). The activities of Nrf2, HO-1, p-p65 and p-IκB were determined by western blotting. The results showed that the model of LPS-induced ALI was successfully replicated, and it was found that PTER could significantly improve the pathological degree of ALI such as sustained the integrity of the lung tissue structure, alleviated pulmonary interstitial edema and alveolar wall thickening, reduced infiltrated inflammatory cells. PTER could decrease the number of inflammatory cells and obviously inhibit the increase of W/D ratio caused by LPS. PTER could also significantly reduce LPS-induced MPO and MDA, and increase LPS-decreased SOD, CAT and GSH-Px in the lungs. In addition, it was also found that PTER has the ability to decrease LPS-induced production of COX-2, iNOS, TNF-α, IL-6 and IL-1β. The underlying mechanism involved in the protective effect of PTER on ALI were via activating Nrf2 and HO-1, and inhibiting the phosphorylation of p65 and IκB. These results suggested that PTER can protect LPS-induced ALI in mice by inhibiting inflammatory response and oxidative stress, which provided evidence that PTER may be a potential therapeutic candidate for LPS-induced ALI intervention.

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Pterostilbene and 4′-Methoxyresveratrol Inhibited Lipopolysaccharide-Induced Inflammatory Response in RAW264.7 Macrophages

Cited by 28 publications

References 34 publications

m6A Reader YTHDF2 Regulates LPS-Induced Inflammatory Response

m6A Reader YTHDF2 Regulates LPS-Induced Inflammatory Response

Hesperidin ameliorates insulin resistance by regulating the IRS1‐GLUT2 pathway via TLR4 in HepG2 cells

Protective Effects of Pterostilbene on Lipopolysaccharide-Induced Acute Lung Injury in Mice by Inhibiting NF-κB and Activating Nrf2/HO-1 Signaling Pathways

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