NLRP3 Inflammasome Activation Is Essential for Paraquat-Induced Acute Lung Injury

Liu, Zhenning; Zhao, Hongyu; Liu, Wei; Li, Tiegang; Wang, Yu; Zhao, Min

doi:10.1007/s10753-014-0048-2

Cited by 59 publications

(46 citation statements)

References 39 publications

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“…In addition, Samantaray et al 33 have shown that MT inhibited inflammation by suppressing the activation of macrophages, microglia, and astrocytes, thus decreasing the level of axonal degeneration after SCI injury. 38,39 In addition, it was reported that Cd could trigger inflammatory cell death via NLRP3 inflammasomes. These results are consistent with those published by Genovese et al 32 who showed that MT treatment could dramatically improve limb functions by playing strong anti-inflammatory roles in an animal model of SCI.…”

Section: Discussionmentioning

confidence: 99%

Melatonin ameliorates spinal cord injury by suppressing the activation of inflammasomes in rats

Shi

Zhi

et al. 2018

J of Cellular Biochemistry

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Background The activation of inflammasomes plays an important role in the pathogenesis of spinal cord injury (SCI). In addition, the administration of melatonin (MT) has been shown to suppress the activation of inflammasomes. In this study, we aimed to investigate the molecular mechanisms underlying the therapeutic effect of MT in the treatment of SCI. Methods Basso‐Beattie‐Bresnahan (BBB) locomotion scaling was conducted to evaluate the therapeutic effect of MT on post‐SCI locomotion recovery. In addition, the measurement of spinal cord water content was performed together with Nissl staining to evaluate the protective effect of MT against SCI. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay, immunohistochemistry (IHC) assay, Western blot analysis, and real‐time polymerase chain reaction (PCR) were also conducted to clarify the molecular mechanisms underlying the therapeutic effect of MT in the treatment of SCI. Results BBB scores of SCI + MT rats were increased compared with the BBB scores of SCI rats, thus confirming the beneficial role of MT treatment in post‐SCI functional recovery. Meanwhile, the administration of MT could alleviate SCI by reducing spinal cord water content and by exerting a neuroprotective effect on motor neurons. Furthermore, in the treatment of SCI, MT also attenuated cell apoptosis. Moreover, the relative expression of NLRP3, interleukin‐1β (IL‐1β), and caspase‐1 were markedly elevated in the SCI group compared with that in the sham group, while the administration of MT reduced the expression of NLRP3 in SCI rats. Conclusions MT treatment accelerated the recovery of SCI by suppressing the activation of inflammasomes.

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Section: Discussionmentioning

confidence: 99%

Melatonin ameliorates spinal cord injury by suppressing the activation of inflammasomes in rats

Shi

Zhi

et al. 2018

J of Cellular Biochemistry

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“…PQ is a strong pneumotoxicant, particularly due to its ability to accumulate in the lung, which is facilitated by alveolar epithelial cells via the polyamine uptake pathway, resulting in ALI (23). Despite the mechanism underlying the development of lung injury by PQ remaining undetermined, previous studies have demonstrated that oxidative and inflammatory mediators induced by PQ may result in tissue injury (24). Current treatments for PQ poisoning primarily consist of anti-inflammatory and anti-oxidative treatments for the attenuation of PQ-induced ALI (25,26).…”

Section: Discussionmentioning

confidence: 99%

Tanshinone IIA attenuates paraquat‑induced acute lung injury by modulating angiotensin‑converting enzyme 2/angiotensin‑(1‑7) in rats

Wang

Niu

et al. 2018

Mol Med Report

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Tanshinone IIA (TIIA) is an active compound that can be isolated from the Chinese herb, Salvia miltiorrhizae Bunge, also known as danshen. Previous studies have demonstrated that TIIA can effectively attenuate bleomycin‑induced pulmonary fibrosis in rats. However, it has not been determined whether TIIA can attenuate paraquat (PQ)‑induced acute lung injury (ALI). In the present study, the protective effects exhibited by TIIA on PQ‑induced ALI, as well as its underlying mechanisms, were investigated using Sprague‑Dawley (SD) rats. ALI animal models using rats were established via administration of PQ. Adult male SD rats were randomly divided into three groups: A control group, a PQ group and a PQ + TIIA group. Total cell count, total protein levels and lactic dehydrogenase (LDH) levels in bronchoalveolar lavage fluid (BALF), as well as myeloperoxidase (MPO) activity in lung tissues were determined. Lung histological alterations were also investigated. Angiotensin converting enzyme 2 (ACE2) and Angiotensin 1‑7 [Ang‑(1‑7)] expression levels in the lung were also analyzed. The results demonstrated that administration of PQ induced marked histological alterations, and markedly increased neutrophil infiltration, lung wet/dry weight ratio, total cell count, protein content and LDH levels in BALF. In addition, PQ was revealed to significantly decrease ACE2 and Ang‑(1‑7) expression levels in lung tissues. However, it was demonstrated that TIIA attenuated these effects. Therefore, the results of the present study suggest that that TIIA may exhibit a therapeutic effect regarding PQ‑induced ALI in rats, and that ACE2 and Ang‑(1‑7) may be involved in the underlying mechanisms of this effect.

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“…Inhibition of ROS production or scavengers of ROS, such as NAD(P) H oxidase inhibitors, can suppress NLRP3 inflammasome activation48. ROS activates NLRP3 inflammasome in paraquat, burn, and hemorrhagic shock-induced ALI104950. It has been reported that TREM-1 activation stimulates intracellular Ca 2+ mobilization11.…”

Section: Discussionmentioning

confidence: 99%

Blocking triggering receptor expressed on myeloid cells-1 attenuates lipopolysaccharide-induced acute lung injury via inhibiting NLRP3 inflammasome activation

Liu

Zhou

et al. 2016

Sci Rep

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Acute lung injury (ALI) is associated with high mortality and uncontrolled inflammation plays a critical role in ALI. TREM-1 is an amplifier of inflammatory response, and is involved in the pathogenesis of many infectious diseases. NLRP3 inflammasome is a member of NLRs family that contributes to ALI. However, the effect of TREM-1 on NLRP3 inflammasome and ALI is still unknown. This study aimed to determine the effect of TREM-1 modulation on LPS-induced ALI and activation of the NLRP3 inflammasome. We showed that LR12, a TREM-1 antagonist peptide, significantly improved survival of mice after lethal doses of LPS. LR12 also attenuated inflammation and lung tissue damage by reducing histopathologic changes, infiltration of the macrophage and neutrophil into the lung, and production of the pro-inflammatory cytokine, and oxidative stress. LR12 decreased expression of the NLRP3, pro-caspase-1 and pro-IL-1β, and inhibited priming of the NLRP3 inflammasome by inhibiting NF-κB. LR12 also reduced the expression of NLRP3 and caspase-1 p10 protein, and secretion of the IL-1β, inhibited activation of the NLRP3 inflammasome by decreasing ROS. For the first time, these data show that TREM-1 aggravates inflammation in ALI by activating NLRP3 inflammasome, and blocking TREM-1 may be a potential therapeutic approach for ALI.

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NLRP3 Inflammasome Activation Is Essential for Paraquat-Induced Acute Lung Injury

Cited by 59 publications

References 39 publications

Melatonin ameliorates spinal cord injury by suppressing the activation of inflammasomes in rats

Melatonin ameliorates spinal cord injury by suppressing the activation of inflammasomes in rats

Tanshinone IIA attenuates paraquat‑induced acute lung injury by modulating angiotensin‑converting enzyme 2/angiotensin‑(1‑7) in rats

Blocking triggering receptor expressed on myeloid cells-1 attenuates lipopolysaccharide-induced acute lung injury via inhibiting NLRP3 inflammasome activation

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