Resveratrol ameliorates LPS-induced acute lung injury via NLRP3 inflammasome modulation

Jiang, Lei; Zhang, Lei; Kang, Kai; Fei, Dongsheng; Gong, Rui; Cao, Yuan; Pan, Shangha; Zhao, Mingran; Zhao, Mingyan

doi:10.1016/j.biopha.2016.09.020

Cited by 105 publications

(73 citation statements)

References 43 publications

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“…Modulation of macrophage subtypes is a promising therapeutic approach in the treatment of many inflammatory diseases such as ALI/ARDS. In the LPS‐induced murine ALI model, Res can effectively attenuate the severity of ALI, and the beneficial effects are associated with lower NLRP3 inflammasome activation and release of IL‐1beta and IL‐18 . However, whether Res suppresses ALI through modulation of macrophage subtypes and whether STAT3/SOCS3 signalling is involved in the therapeutic effects remains unknown.…”

Section: Discussionmentioning

confidence: 99%

“…Res or Res‐curcumin hybrids can significantly attenuate disease severity of ALI, accompanied with lower production of pro‐inflammatory cytokines and chemokines, such as TNF‐alpha, IL‐1beta, IL‐6, IL‐12, IL‐33, MIP‐2 and IL‐18. In contrast, the anti‐inflammatory cytokines and molecular mediators, such as IL‐10, heme oxygenase‐1 (HO‐1),Nrf2 (nuclear factor‐erythroid 2 related factor) and SOD (superoxide dismutase), were increased in the Res‐treated animal models . The beneficial effects may be associated with up‐regulation and activation of SIRT1, a nicotinamide adenine dinucleotide (NAD+‐dependent deacetylase sirtuin 1) .…”

Section: Introductionmentioning

confidence: 99%

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Resveratrol decreases CD45⁺CD206⁻ subtype macrophages in LPS‐induced murine acute lung injury by SOCS3 signalling pathway

Chen

et al. 2019

J Cellular Molecular Medi

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Acute lung injury/acute respiratory distress syndrome (ALI/ARDS) are life‐threatening condition in critically ill patients. Resveratrol (Res), a natural polyphenol, has therapeutic effect in animal model with ALI; however, whether Res attenuates ALI through modulation of macrophage phenotypes in the animal model remains unknown. We in this study treated LPS‐induced murine ALI with 30 mg/kg Res and observed significantly reduced severity of ALI in the Res‐treated mice 48 hours after Res treatment. Neutrophil infiltrates were significantly reduced, accompanied with lower infiltration of CD45+Siglec F− phenotype macrophages, but higher population of CD45+Siglec F+ and CD45+CD206+ alternatively activated macrophages (M2 cells) in the Res‐treated mice with ALI. In addition, the expression of IL‐1beta and CXCL15 cytokines was suppressed in the treated mice. However, Res treatment in mice with myeloid cell‐restricted SOCS3 deficiency did not significantly attenuate ALI severity and failed to increase population of both CD45+Siglec F+ and CD45+CD206+ M2 subtype macrophages in the murine ALI. Further studies in wild‐type macrophages revealed that Res treatment effectively reduced the expression of IL‐6 and CXCL15, and increased the expression of arginase‐1, SIRT1 and SOCS3. However, macrophages’ lack of SOCS3 expression were resistant to the Res‐induced suppression of IL‐6 and CXCL15 in vitro. Thus, we conclude that Res suppressed CD45+Siglec F− and CD45+CD206− M1 subtype macrophages through SOCS3 signalling in the LPS‐induced murine ALI.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Resveratrol decreases CD45⁺CD206⁻ subtype macrophages in LPS‐induced murine acute lung injury by SOCS3 signalling pathway

Chen

et al. 2019

J Cellular Molecular Medi

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“…In response to ROS, Txnip detaches from thioredoxin (Trx), which is composed of two isoforms, including the cytosolic Trx-1 and mitochondrial Trx-2, and binds to nucleotide-binding domain-like receptor protein 3 (NLRP3), resulting in NLRP3 inflammasome activation [16], [17]. Activation of NLRP3 inflammasome, including NOD like receptor, NLRP3 protein, the adaptor ASC protein and caspase-1, result in the maturation and release of pro-inflammatory cytokines, IL-1β and IL-18 which also plays a significant role in the development of ALI [18], [19].…”

Section: Introductionmentioning

confidence: 99%

Xanthohumol ameliorates lipopolysaccharide (LPS)-induced acute lung injury via induction of AMPK/GSK3β-Nrf2 signal axis

et al. 2017

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Abundant natural flavonoids can induce nuclear factor-erythroid 2 related factor 2 (Nrf2) and/or AMP-activated protein kinase (AMPK) activation, which play crucial roles in the amelioration of various inflammation- and oxidative stress-induced diseases, including acute lung injury (ALI). Xanthohumol (Xn), a principal prenylflavonoid, possesses anti-inflammation and anti-oxidant activities. However, whether Xn could protect from LPS-induced ALI through inducing AMPK/Nrf2 activation and its downstream signals, are still poorly elucidated. Accordingly, we focused on exploring the protective effect of Xn in the context of ALI and the involvement of underlying molecular mechanisms. Our findings indicated that Xn effectively alleviated lung injury by reduction of lung W/D ratio and protein levels, neutrophil infiltration, MDA and MPO formation, and SOD and GSH depletion. Meanwhile, Xn significantly lessened histopathological changes, reactive oxygen species (ROS) generation, several cytokines secretion, and iNOS and HMGB1 expression, and inhibited Txnip/NLRP3 inflammasome and NF-κB signaling pathway activation. Additionally, Xn evidently decreased t-BHP-stimulated cell apoptosis, ROS generation and GSH depletion but increased various anti-oxidative enzymes expression regulated by Keap1-Nrf2/ARE activation, which may be associated with AMPK and GSK3β phosphorylation. However, Xn-mediated inflammatory cytokines and ROS production, histopathological changes, Txnip/NLRP3 inflammasome and NF-κB signaling pathway in WT mice were remarkably abrogated in Nrf2-/- mice. Our experimental results firstly provided a support that Xn effectively protected LPS-induced ALI against oxidative stress and inflammation damage which are largely dependent upon upregulation of the Nrf2 pathway via activation of AMPK/GSK3β, thereby suppressing LPS-activated Txnip/NLRP3 inflammasome and NF-κB signaling pathway.

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“…These effects of NR and NMN appear to be largely mediated by SIRT1 and/ or SIRT3 [117, 121, 124]. Not surprisingly, resveratrol, the polyphenol present in the skin of grapes, another sirtuin activator, also inhibits NLRP3 inflammasome activation in mice by preserving mitochondrial function, and protects against hepatosteatosis, renal inflammation and LPS-induced lung injury [125–127]. Interestingly, recent evidence suggests that resveratrol activates sirtuins indirectly by increasing NAD + levels in an AMPK-dependent manner [128].…”

Section: Strategies and Therapeutics To Inhibit The Nlrp3 Inflammasomementioning

confidence: 99%

The role of caloric load and mitochondrial homeostasis in the regulation of the NLRP3 inflammasome

Traba

Sack

2016

Cell. Mol. Life Sci.

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Sterile inflammation is a cornerstone of immune activation in obesity and type 2 Diabetes Mellitus. The molecular underpinnings of this inflammation include nutrient excess-mediated activation of the innate immune NLRP3 inflammasome. At the same time, disruption of mitochondrial integrity is emerging as an integral control node in NLRP3 inflammasome activation and is also associated with caloric overload conditions including obesity and diabetes. Conversely, caloric restriction and fasting mimetic interventions alleviate these caloric excess-linked diseases and reduce inflammation and the NLRP3 inflammasome. The objective of this review is to integrate the findings linking mitochondrial integrity to the activation of the NLRP3 inflammasome and to evaluate how caloric restriction or caloric restriction mimetic compounds may play a role in attenuating the NLRP3 inflammasome and sterile inflammation.

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Resveratrol ameliorates LPS-induced acute lung injury via NLRP3 inflammasome modulation

Cited by 105 publications

References 43 publications

Resveratrol decreases CD45⁺CD206⁻ subtype macrophages in LPS‐induced murine acute lung injury by SOCS3 signalling pathway

Resveratrol decreases CD45⁺CD206⁻ subtype macrophages in LPS‐induced murine acute lung injury by SOCS3 signalling pathway

Xanthohumol ameliorates lipopolysaccharide (LPS)-induced acute lung injury via induction of AMPK/GSK3β-Nrf2 signal axis

The role of caloric load and mitochondrial homeostasis in the regulation of the NLRP3 inflammasome

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Resveratrol ameliorates LPS-induced acute lung injury via NLRP3 inflammasome modulation

Cited by 105 publications

References 43 publications

Resveratrol decreases CD45+CD206− subtype macrophages in LPS‐induced murine acute lung injury by SOCS3 signalling pathway

Resveratrol decreases CD45+CD206− subtype macrophages in LPS‐induced murine acute lung injury by SOCS3 signalling pathway

Xanthohumol ameliorates lipopolysaccharide (LPS)-induced acute lung injury via induction of AMPK/GSK3β-Nrf2 signal axis

The role of caloric load and mitochondrial homeostasis in the regulation of the NLRP3 inflammasome

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Product

Resources

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Resveratrol decreases CD45⁺CD206⁻ subtype macrophages in LPS‐induced murine acute lung injury by SOCS3 signalling pathway

Resveratrol decreases CD45⁺CD206⁻ subtype macrophages in LPS‐induced murine acute lung injury by SOCS3 signalling pathway