Smiglaside A ameliorates LPS-induced acute lung injury by modulating macrophage polarization via AMPK-PPARγ pathway

Wang, Yurong; Xu, Yuan; Zhang, Pingping; Ruan, Wenchen; Zhang, Luyong; Yuan, Shengtao; Pang, Tao; Jia, Ai‐Qun

doi:10.1016/j.bcp.2018.09.002

Cited by 62 publications

(36 citation statements)

References 46 publications

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“…In vitro experiments further proved that pharmacological inhibition or genetic ablation of EZH2 could inhibit M1 polarization while promoting M2 phenotype switch in alveolar macrophage cell line. Large amount of studies have suggested a crucial role of miRNAs in regulating macrophage polarization in ARDS [21,22,26,27] . In the current study, we found a lower expression of let-7c in the alveolar macrophages with a remarkable reservation after 3-DZNeP treatment, which is concordant with a recent study showing that let-7c suppresses polarization of macrophages to the M1 phenotype and enhances M2 polarization via targeting C/EBP-delta in sepsis [21] .…”

Section: Discussionmentioning

confidence: 99%

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Inhibition of EZH2 prevents acute respiratory distress syndrome (ARDS)-associated pulmonary fibrosis by regulating the macrophage polarization phenotype

Bao

Liu

et al. 2020

Preprint

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Background: We recently reported histone methyltransferase enhancer of zeste homolog 2 (EZH2) as a key epigenetic regulator that contributes to the dysfunction of innate immune responses to sepsis and subsequent lung injury by mediating the imbalance of macrophage polarization. However, the role of EZH2 in acute respiratory distress syndrome (ARDS)-associated fibrosis remains poorly understood. Methods: In this study, we investigated the role and mechanisms of EZH2 in pulmonary fibrosis in a murine model of LPS-induced ARDS and in ex-vivo cultured alveolar macrophages (MH-S) and mouse lung epithelial cell line (MLE-12) by using 3-deazaneplanocin A (3-DZNeP) and EZH2 the small interfering (si) RNA. Results: We found that treatment with 3-DZNeP significantly ameliorated the LPS-induced direct lung injury and fibroproliferation by blocking the epithelial to mesenchymal transition (EMT) through transforming growth factor-β1 (TGF-β1)/Smad signaling pathway and regulating shift of macrophage phenotypes. In the ex-vivo polarized alveolar macrophages cells, treatment with EZH2 siRNA or 3-DZNeP suppressed the M1 while promoted the M2 macrophage differentiation through modulating the STAT/SOCS signaling pathway and activating PPAR-γ. Moreover, we identified that blockade of EZH2 with 3-DZNeP suppressed EMT in co-cultured bronchoalveolar lavage fluid (BALF) and mouse lung epithelial cell line through down-regulation of TGF-β1, TGF-βR1, Smad2 while up-regulation of Smad7 expression. Conclusions: These results indicate that EZH2 is involved in the pathological process of ARDS-associated pulmonary fibrosis. Targeting EZH2 may be a potential therapeutic strategy to prevent and treat pulmonary fibrosis post ARDS.

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Section: Discussionmentioning

confidence: 99%

“…5E, 5F). Previous studies have also suggested that the transcription factor PPAR-γ plays a pivotal role in the M1/M2 balance [16,22] . As shown in Fig.…”

Section: -Dznep or Ezh2 Sirna Suppressed Stat1 Pathway In The M1-polmentioning

confidence: 97%

Inhibition of EZH2 prevents acute respiratory distress syndrome (ARDS)-associated pulmonary fibrosis by regulating the macrophage polarization phenotype

Bao

Liu

et al. 2020

Preprint

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“…The quantitative real-time PCR procedures were performed according to previous studies [ 4 ], with some modifications. RAW 264.7 cells were seeded into 6 well-plates for 24 h at 37 °C and 5% CO 2 .…”

Section: Methodsmentioning

confidence: 99%

“…Although inflammation is indispensable and important for homeostasis and human health, excessive inflammation can potentially cause damage for the host organisms and induce many diseases, such as cancer, rheumatoid arthritis, diabetes, septic shock, and cardiovascular diseases due to the toxic effects of several inflammatory factors [ 1 , 3 ]. Macrophages, which have two distinguishable phenotypes, classical/pro-inflammatory (M1) and alternative/anti-inflammatory (M2), play an important role in the immune responses to infection in the inflammatory process [ 4 , 5 ]. Lipopolysaccharide (LPS), one of the outer cell membrane components of gram-negative bacteria, is a famous endotoxin which can activate macrophages to produce many kinds of inflammatory cytokines such as tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6) etc.…”

Section: Introductionmentioning

confidence: 99%

Anti-inflammatory activity of 3-cinnamoyltribuloside and its metabolomic analysis in LPS-activated RAW 264.7 cells

Wang

Guan

Yang

et al. 2020

BMC Complement Med Ther

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Background Inflammation is a response to tissue injuries, which is indispensable and important for human health, but excessive inflammation can potentially cause damage to the host organisms. Camellia nitidissima Chi, one traditional medicinal and edible plant in China, was reported to exhibit anti-inflammation capability. Hence, this study was conducted to isolate the bioactive compounds from the flowers of C. nitidissima Chi and evaluate their anti-inflammatory activity. Methods The phytochemicals from the flowers of C. nitidissima Chi were isolated and purified by silica gel, Sephadex LH-20 gel, C18 reversed silica gel, semi-preparative HPLC, and identified by the spectrum technologies. The anti-inflammatory activity of isolated compounds was evaluated using cultured macrophage RAW 264.7 cells. Whereafter the potential metabolic mechanism of the anti-inflammatory activity of the bioactive compound was investigated by a 1H-NMR based metabolomics approach. The metabolites in 1H-NMR spectra were identified by querying the Human Metabolome Database and Madison Metabolomics Consortium Database online. And the multivariate statistical analysis was performed to evaluate the variability of metabolites among samples and between sample classes. Results The compound isolated from the flowers of C. nitidissima Chi was identified as 3-cinnamoyltribuloside (3-CT). 3-CT could inhibit the NO production and the mRNA expression of iNOS involved in lipopolysaccharide (LPS)-activated RAW 264.7 cells. Moreover, 3-CT could inhibit the expression of a series of inflammatory cytokines, including TNF-α, IL-1β, and IL-6, both at the mRNA level and protein level. The 1H-NMR based metabolomics approach was applied to investigate the potential metabolic mechanism of the anti-inflammatory activity of 3-CT. Thirty-five metabolites were identified and assigned. Orthogonal signal correction partial least-squares discriminant analysis (OSC-PLS-DA) of the 1H-NMR data showed 3-CT could balance the significant changes in many endogenous metabolites (e.g., choline, glucose, phenylalanine) induced by LPS in RAW 264.7 cells, which related to cholinergic anti-inflammatory pathway, oxidative stress, energy metabolism, and amino acids metabolism. Conclusion 3-CT, isolated from the flowers of C. nitidissima Chi, had potent anti-inflammatory activity in LPS-activated RAW 264.7 cells. Furthermore, our results indicated that 3-CT had effects on the cholinergic anti-inflammatory pathway, oxidative stress, energy metabolism, and amino acids metabolism in LPS-activated RAW 264.7 cells.

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“…For example, curcumin can promote macrophages toward M2-like phenotype to ameliorate liver fibrosis, and it also assists wound healing [76]. Smiglaside A and Ginsenoside Rb3 have protective functions against acute lung injury via inducing M2-like macrophage polarization [77,78]. These findings may throw a new light for the regulatory mechanisms of Chinese medicines and promote their applications in health and diseases.…”

Section: Other Chinese Medicinementioning

confidence: 99%

Polarization of Tumor-Associated Macrophages by Chinese Medicine Intervention: Mechanisms and Applications

Lu¹,

Tan²,

Wang³

et al. 2020

Macrophage Activation - Biology and Disease

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Macrophage polarization is a spectrum of phenotypes and generally can be classified into two states: (1) classically activated or M1 macrophages, which can be driven by lipopolysaccharide (LPS) alone or in association with Th1 cytokines and produce pro-inflammatory cytokines such as TNF-α, IL-6 and, IL-12, and (2) alternatively activated M2 macrophages, which can be promoted by Th2 mediators IL-4 and IL-13 and produce anti-inflammatory cytokines such as TGF-β and IL-10. Current studies have found that the phenotypic switch between M1 and M2 macrophages governs the fate of an organ in inflammation or injury. The imbalance of M1/M2 polarization is closely involved in various pathological processes and is becoming a potential target for therapeutic strategies. Traditional Chinese medicine is an integrated healthcare system composed of many practices and is characterized by multi-target, multi-level, and coordinated intervention effects. Chinese medicines nowadays are applied to regulate phenotype polarization of macrophages to improve the microenvironment, thus ameliorating or even eliminating the symptoms. In this chapter, we will discuss the molecular mechanisms of macrophage polarization, their roles in health and disease, and the intervention with Chinese medicines to modulate the polarization of macrophages in tumor microenvironment (TME) for therapeutic purpose.

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Smiglaside A ameliorates LPS-induced acute lung injury by modulating macrophage polarization via AMPK-PPARγ pathway

Cited by 62 publications

References 46 publications

Inhibition of EZH2 prevents acute respiratory distress syndrome (ARDS)-associated pulmonary fibrosis by regulating the macrophage polarization phenotype

Inhibition of EZH2 prevents acute respiratory distress syndrome (ARDS)-associated pulmonary fibrosis by regulating the macrophage polarization phenotype

Anti-inflammatory activity of 3-cinnamoyltribuloside and its metabolomic analysis in LPS-activated RAW 264.7 cells

Polarization of Tumor-Associated Macrophages by Chinese Medicine Intervention: Mechanisms and Applications

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