Dexmedetomidine Attenuates Lung Injury in Toxic Shock Rats by Inhibiting Inflammation and Autophagy

Li, Zhibing; Li, Guang‐Cai; Qin, Jing

doi:10.1016/j.arcmed.2020.11.001

Cited by 10 publications

(8 citation statements)

References 22 publications

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“…Recent research has revealed that DEX is effective in improving pulmonary vascular permeability in animal studies and reduces inflammatory cytokine production in lung tissue, resulting in reduced inflammation [ 12 , 13 ]. As Li et al show that DEX can suppress lung injury in toxic shock rats by inhibiting inflammation and autophagy [ 14 ], DEX improves lung function by promoting inflammation resolution in patients undergoing totally thoracoscopic cardiac surgery [ 15 ]. It shows that the protective effect of DEX is closely related to the inhibition of inflammation.…”

Section: Discussionmentioning

confidence: 99%

Dexmedetomidine Attenuates LPS-Stimulated Alveolar Type II Cells’ Injury through Upregulation of miR-140-3p and Partial Suppression of PD-L1 Involving Inactivating JNK-Bnip3 Pathway

Chen

Lai

et al. 2022

Canadian Respiratory Journal

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Dexmedetomidine (DEX), which is reported to be a newly discovered, novel α-2 adrenoceptor agonist, is known to exhibit anti-inflammatory properties in several diseases. DEX regulates inflammation-related signaling pathways and genes through interactions with several miRNAs. This study verified that expression levels of miR-140-3p were diminished when alveolar type II cells were exposed to LPS. However, the levels of miR-140-3p were confirmed as showing an increase with DEX treatment. These observations revealed that the expression of miR-140-3p was related to the beneficial effects that accompanied the DEX treatment of LPS-induced ALI. In addition, PD-1/PD-L1 expression increased extensively when RLE-6TN cells were induced by LPS. The increased expression was reduced after treatment with DEX. Thus, it appears that the PD-L1 expression was targeted directly by miR-140-3p, resulting in the partial repression of PD-L1 levels, which involved the inhibition of p-JNK and Bnip3 expression. Therefore, DEX was shown to inhibit the PD-L1 expression by promoting partially increased miR-140-3p levels in RLE-6TN cells. DEX also inactivated the JNK-Bnip3 pathway, resulting in the inhibition of inflammation and alleviating alveolar type II cell injury.

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Section: Discussionmentioning

confidence: 99%

Dexmedetomidine Attenuates LPS-Stimulated Alveolar Type II Cells’ Injury through Upregulation of miR-140-3p and Partial Suppression of PD-L1 Involving Inactivating JNK-Bnip3 Pathway

Chen

Lai

et al. 2022

Canadian Respiratory Journal

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“…A data collection table was applied to extract the key data from the relevant studies, including the first author’s name, publication year, geographical distribution, cell/animal model, types of organ injury, DEX administration, autophagy status, associated genes or pathways, and the main findings of the included studies. Finally, 24 studies [ 21 , 27 – 30 , 41 – 59 ] were included. Among these, 14, 4, 3, and 3 eligible studies reported cerebral injury, myocardial injury, kidney injury, and lung injury, respectively.…”

Section: Introductionmentioning

confidence: 99%

“…2018 [ 58 ] Mouse Lipopolysaccharide-induced acute lung injury Intravenously injected, 50 μg/kg Inhibited Inhibition of the TLR4-NF-κB pathway DEX protects against acute lung injury via reducing the inflammatory response and inhibiting autophagy-related proteins and signaling pathway Li et al. 2021 [ 59 ] Rat Toxic shock-induced lung injury Intraperitoneally, 50 μg/kg Inhibited Decreasing the expression of pERK1/2 protein DEX protects against lung injury by inhibiting autophagy and inflammation iPSC cell human induced pluripotent stem cell …”

Section: Introductionmentioning

confidence: 99%

“…Mechanistically, the lung-protective effects developed by DEX might be correlated to the autophagy-associated signaling pathways. To date, three studies [ 30 , 58 , 59 ] have reported the roles of autophagy in the action of DEX attenuating lung injury. All these studies indicated that the autophagic response was inhibited when treated with DEX in an animal model of lung injury.…”

Section: Introductionmentioning

confidence: 99%

“…Based on a toxic shock-induced lung injury rat model, Li et al. [ 59 ] found that DEX remarkably protected against lung injury by inhibiting autophagy and inflammation by decreasing the expression of pERK1/2 protein. The administration of DEX was the same in the above studies, viz.…”

Section: Introductionmentioning

confidence: 99%

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Protective effects of dexmedetomidine in vital organ injury: crucial roles of autophagy

Zhao

Wu²,

Lin

et al. 2022

Cell Mol Biol Lett

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Vital organ injury is one of the leading causes of global deaths. Accumulating studies have demonstrated that dexmedetomidine (DEX) has an outstanding protective effect on multiple organs for its antiinflammatory and antiapoptotic properties, while the underlying molecular mechanism is not clearly understood. Autophagy, an adaptive catabolic process, has been found to play a crucial role in the organ-protective effects of DEX. Herein, we present a first attempt to summarize all the evidence on the proposed roles of autophagy in the action of DEX protecting against vital organ injuries via a comprehensive review. We found that most of the relevant studies (17/24, 71%) demonstrated that the modulation of autophagy was inhibited under the treatment of DEX on vital organ injuries (e.g. brain, heart, kidney, and lung), but several studies suggested that the level of autophagy was dramatically increased after administration of DEX. Albeit not fully elucidated, the underlying mechanisms governing the roles of autophagy involve the antiapoptotic properties, inhibiting inflammatory response, removing damaged mitochondria, and reducing oxidative stress, which might be facilitated by the interaction with multiple associated genes (i.e., hypoxia inducible factor-1α, p62, caspase-3, heat shock 70 kDa protein, and microRNAs) and signaling cascades (i.e., mammalian target of rapamycin, nuclear factor-kappa B, and c-Jun N-terminal kinases pathway). The authors conclude that DEX hints at a promising strategy in the management of vital organ injuries, while autophagy is crucially involved in the protective effect of DEX.

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Clinical Use of Adrenergic Receptor Ligands in Acute Care Settings

Langnas,

Maze

2024

Handbook of Experimental Pharmacology

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Dexmedetomidine Attenuates Lung Injury in Toxic Shock Rats by Inhibiting Inflammation and Autophagy

Cited by 10 publications

References 22 publications

Dexmedetomidine Attenuates LPS-Stimulated Alveolar Type II Cells’ Injury through Upregulation of miR-140-3p and Partial Suppression of PD-L1 Involving Inactivating JNK-Bnip3 Pathway

Dexmedetomidine Attenuates LPS-Stimulated Alveolar Type II Cells’ Injury through Upregulation of miR-140-3p and Partial Suppression of PD-L1 Involving Inactivating JNK-Bnip3 Pathway

Protective effects of dexmedetomidine in vital organ injury: crucial roles of autophagy

Clinical Use of Adrenergic Receptor Ligands in Acute Care Settings

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