Ventilator-induced lung injury is alleviated by inhibiting NLRP3 inflammasome activation

Liu, Huan; Gu, Chao; Liu, Mengjie; Liu, Ge; Wang, Dong; Liu, Xiaobin; Wang, Yuelan

doi:10.1016/j.molimm.2019.03.011

Cited by 35 publications

(34 citation statements)

References 28 publications

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“…NLRP3 is a recently discovered inflammatory pathway associated with lung disease, which increases the permeability of cells and induces the production of pro‐inflammatory cytokines . It has been proved that ventilator can induce lung injury by activating NLRP3 inflammasome . The cleavage of caspase‐1 and maturation of IL‐1β are the markers of NLRP3 inflammasome activation, thus the expression of NLRP3, cleaved caspase‐1 and mature IL‐1β were measured in this study, as shown in Figure , the protein of NLRP3, cleaved caspase‐1 and 17‐kDa mature IL‐1β increased significantly ( P < .01) in a dose‐dependent manner in nickel‐treated BEAS‐2B cells.…”

Section: Resultsmentioning

confidence: 76%

Resveratrol protects human bronchial epithelial cells against nickel‐induced toxicity via suppressing p38 MAPK, NF‐κB signaling, and NLRP3 inflammasome activation

Cao

Tian

et al. 2020

Environmental Toxicology

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Nickel is a common environmental pollutant that can impair the lung, but the underlying mechanisms have not yet been fully elucidated. Furthermore, natural products are generally used to inhibit cell damage induced by heavy metal. Resveratrol possesses wide biological activities, including anti‐inflammation and antioxidative stress. This study was conducted to explore the toxicity of nickel on human bronchial epithelial (BEAS‐2B) cells and evaluate the protective effect of resveratrol. The results showed that nickel could induce cell apoptosis, increase oxidative stress, and promote the expression of pro‐inflammatory cytokines, including tumor necrosis factor‐α, interleukin (IL)‐1β, IL‐6, IL‐8, C‐reaction protein. Western blot analysis showed that nickel activated p38 mitogen‐activated protein kinase (MAPK), nuclear factor‐kappa B, and nucleotide‐binding oligomerization domain‐like receptor pyrin‐domain‐containing protein 3 pathways, while resveratrol could reverse these effects. Our results suggested that resveratrol could protect BEAS‐2B cells from nickel‐induced cytotoxicity. Therefore, resveratrol is a potential chemopreventive agent against nickel‐induced lung disease.

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Section: Resultsmentioning

confidence: 76%

Resveratrol protects human bronchial epithelial cells against nickel‐induced toxicity via suppressing p38 MAPK, NF‐κB signaling, and NLRP3 inflammasome activation

Cao

Tian

et al. 2020

Environmental Toxicology

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“…IL-1β and IL-18 were confirmed to be products of NLRP3 inflammasome activation [19]. Furthermore, current studies have demonstrated that NLRP3 inflammasome activation plays a key role in the pathogenesis of VILI in a mouse model [17,18]. Therefore, lung-protective ventilation may inhibit inflammatory responses by inhibiting activation of the NLRP3 inflammasome during OLV.…”

Section: Discussionmentioning

confidence: 82%

“…Recently, researchers demonstrated that NLRP3 inflammasome activation is important for exacerbating VILI [17,18]. The activation of the NLRP3 inflammasome produces IL-1β and IL-18 [19].…”

Section: Changes In Il-1β and Il-18 In The Balf And Plasmamentioning

confidence: 99%

The Effects of One-lung Ventilation on the Production of Endogenous Melatonin and NLRP3 Inflammasome-Related Inflammatory Cytokines in Patients Undergoing Laparoscopic Esophagectomy: A Prospective Randomized Double-Blind Controlled Study

Wang¹,

Li²,

Huang³

et al. 2020

Preprint

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Background: NLRP3 inflammasome has been confirmed to play a pivotal role in ventilator-induced lung injury (VILI), while exogenous melatonin can attenuate VILI by inhibiting NLRP3 inflammasome activation in mouse model. However, the relationship between endogenous melatonin and the NLRP3 inflammasome-related inflammatory cytokines in VILI induced by one-lung ventilation (OLV) remains unknown. In this study, we aimed to reveal the relationship between the NLRP3 inflammasome-related inflammatory cytokines: interleukin (IL)-1β, IL-18 and endogenous melatonin in OLV-induced VILI during esophageal cancer surgery.Methods: Twenty-eight patients were randomized to receive “conventional” ventilation (Vt=8 mL/kg) or lung protective ventilation (Vt=5 mL/kg along with 5 cm H 2 O positive end-expiratory pressure (PEEP)). Respiratory variables were evaluated. IL-1β, IL-18 and melatonin in bronchoalveolar lavage fluid (BALF) and plasma were measured.Results: we found that lung protective ventilation during OLV decreased peak airway pressure (Ppeak), plateau airway pressure (Pplat) and driving pressure (ΔP) compared with that in “conventional” ventilation group. Moreover, lung protective ventilation inhibited polymorphonuclear (PMN) cells invasion into BALF. Likewise, lung protective ventilation not only suppressed alveolar and plasma IL-1β secretion, but also reduced increased production of IL-18 in both BALF and plasma after OLV. Furthermore, we found that both alveolar and plasma endogenous melatonin levels in “conventional” ventilation group were lower than that in lung protection group.Conclusion: Taken together, the present study suggested that lung protective ventilation during OLV prevented VILI via suppressing NLRP3 inflammasome-related inflammatory cytokines secretion and restoring the level of endogenous melatonin in patients.Trial registration: the Chinese Clinical Trial Registry, ChiCTR1900026190. Registered 25 September 2019, http://www.chictr.org.cn/edit.aspx?pid=34677&htm=4

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“…Furthermore, current studies have demonstrated that NLRP3 in ammasome activation plays a key role in the pathogenesis of VILI in a mouse model [25,26]. Therefore, lung protective ventilation may inhibit in ammatory responses by inhibiting the activation of the NLRP3 in ammasome.…”

Section: Discussionmentioning

confidence: 87%

The Effects of Protective Ventilation on the Production of Endogenous Melatonin and Prognosis in Patients Undergoing Esophageal Cancer Surgery: A Prospective Randomized Double-Blind Controlled Study

Wang

Huang

et al. 2020

Preprint

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Background: Exogenous melatonin exerts a similar effect to protective ventilation on attenuating ventilator-induced lung injury (VILI) by inhibiting NLRP3 inflammasome activation in mouse model. However, the effect of protective ventilation on the production of endogenous melatonin and prognosis in patients undergoing esophageal cancer surgery remains unknown. In this study, we aimed to reveal the effects of protective ventilation on the production of endogenous melatonin, interleukin (IL)-1β, IL-18 and major complications in patients undergoing esophageal cancer surgery. Methods: Eight-eight patients were randomized to receive “conventional” ventilation (Vt=10 mL/kg) or lung protective ventilation [Vt=5 mL/kg along with 5 cm of H2O positive end-expiratory pressure (PEEP)]. IL-1β, IL-18 and melatonin levels in bronchoalveolar lavage fluid (BALF) and serum were measured. Respiratory variables and outcomes were evaluated.Results: Lung protective ventilation decreased the peak airway pressure (Ppeak), plateau airway pressure (Pplat) and driving pressure (ΔP) compared with the “conventional” ventilation group. Lung protective ventilation inhibited polymorphonuclear (PMN) cells invasion into the BALF (P=0.000). Likewise, lung protective ventilation suppressed alveolar and serum IL-1β and IL-18 secretion after mechanical ventilation. Furthermore, lung protective ventilation resulted in a decrease in the inhibition of endogenous MT production compared to “conventional” ventilation (P=0.000). In addition, lung protective ventilation reduced the incidence of postoperative pulmonary complications (P=0.04) and the rate of major postoperative complications (P=0.023).Conclusions: Taken together, lung protective ventilation for esophageal cancer surgery suppressed the secretion of IL-1β, IL-18 and restored the endogenous melatonin level. Meanwhile, lung protective ventilation improved postoperative outcomes after esophageal cancer surgery.Trial registration: The Chinese Clinical Trial Registry, ChiCTR1900026190. Registered 25 September 2019, http://www.chictr.org.cn/edit.aspx?pid=34677&htm=4

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Ventilator-induced lung injury is alleviated by inhibiting NLRP3 inflammasome activation

Cited by 35 publications

References 28 publications

Resveratrol protects human bronchial epithelial cells against nickel‐induced toxicity via suppressing p38 MAPK, NF‐κB signaling, and NLRP3 inflammasome activation

Resveratrol protects human bronchial epithelial cells against nickel‐induced toxicity via suppressing p38 MAPK, NF‐κB signaling, and NLRP3 inflammasome activation

The Effects of One-lung Ventilation on the Production of Endogenous Melatonin and NLRP3 Inflammasome-Related Inflammatory Cytokines in Patients Undergoing Laparoscopic Esophagectomy: A Prospective Randomized Double-Blind Controlled Study

The Effects of Protective Ventilation on the Production of Endogenous Melatonin and Prognosis in Patients Undergoing Esophageal Cancer Surgery: A Prospective Randomized Double-Blind Controlled Study

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