Dexmedetomidine inhibits the secretion of high mobility group box 1 from lipopolysaccharide-activated macrophages In vitro

Chang, Yulin; Huang, Xiaojing; Liu, Zhaohui; Han, Guofeng; Huang, Lanqing; Xiong, Yang; Wang, Zhengping

doi:10.1016/j.jss.2012.07.017

Cited by 46 publications

(29 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Several in vivo and in vitro researches have showed that Dex has protective effect against lung injury induced by various pathological factors [18-21]. According to our results, Dex treatment significantly reduced the number of inflammatory cells in BALF, W/D weight ratio and ameliorated the pathologic changes in the lung as compared with hyperoxia group.…”

Section: Discussionsupporting

confidence: 63%

Dexmedetomidine Alleviates Hyperoxia-Induced Acute Lung Injury via Inhibiting NLRP3 Inflammasome Activation

Zhang¹,

Wu²,

Yang³

et al. 2017

Cell Physiol Biochem

View full text Add to dashboard Cite

Background/Aims: Dexmedetomidine (Dex), a specific agonist of α2-adrenoceptor, has been reported to have extensive pharmacological effects. In this study, we focused on the protective effect of Dex on hyperoxia-induced acute lung injury and further explored its possible molecular mechanisms. Methods: The model of hyperoxia-induced acute lung injury was established by continuous inhalation of oxygen (FiO2= 0.90) for 7 d in neonatal rats in vivo. The in vitro experiments were carried out in LPS/ATP or hyperoxia-treated RAW264.7 cells. ELISA, western blot, TUNEL staining, and immunohistochemistry staining assays were performed and the commercial kits were used to assess the beneficial effect of Dex on hyperoxia-induced acute lung injury. Results: According to our results, Dex treatment attenuated hyperoxia-induced acute lung injury via decreasing the lung wet/dry(W/D) weight ratio and mitigating pathomorphologic changes. Moreover, the oxidative stress injury, inflammatory reaction, and apoptosis in lung epithelial cells were inhibited by Dex treatment. In addition, the activation of NLRP3 inflammasome was restrained by Dex both in lung tissue in vivo and RAW264.7 cells in vitro. Conclusion: These data provide evidence that Dex may ameliorate hyperoxia-induced acute lung injury, which suggests a potential clinical application of Dex in long-term supplemental oxygen therapy.

show abstract

Section: Discussionsupporting

confidence: 63%

Dexmedetomidine Alleviates Hyperoxia-Induced Acute Lung Injury via Inhibiting NLRP3 Inflammasome Activation

Zhang¹,

Wu²,

Yang³

et al. 2017

Cell Physiol Biochem

View full text Add to dashboard Cite

show abstract

“…Thus, our study supports the hypothesis that ketamine inhibits the MAPK signaling pathway and regulates the translocation of HMGB1 from the nucleus to the cytoplasm. Previous studies have also confirmed that nuclear factor-kappaB [6,27,31,32] and TLR4 [40,41] are involved in regulating the release of inflammatory cytokines. Therefore, the possible mechanism by which ketamine reduces HMGB1 in sepsis is as follows: LPS binds to LPS binding protein along with CD14, a recognition molecule for LPS, which activates TLR4.…”

Section: Discussionmentioning

confidence: 84%

“…The viability of RAW264.7 cells was determined using the Cell Counting Kit-8 Assay kit (Beyotime, Jiangsu, China), as previously reported [27]. RAW264.7 cells were plated at a density of 1 Â 10 4 cells/well in 96-well plates in 100 mL DMEM.…”

Section: Cell Counting Kit-8 Assaymentioning

confidence: 99%

RETRACTED: Ketamine reduces lipopolysaccharide-induced high-mobility group box-1 through heme oxygenase-1 and nuclear factor erythroid 2-related factor 2/ p38 mitogen-activated protein kinase

Wang

Meng

Zhang

et al. 2015

Journal of Surgical Research

View full text Add to dashboard Cite

“…Guanabenz has been reported not only to inhibit PP1, but also to function as α 2 -adrenergic receptor agonist. 23) Several reports suggested that adrenergic receptor agonists blocked the activation of NF-κB, 28,29) suggesting that guanabenz might suppress the activation of NF-κB through both PP1 inhibition and adrenergic receptor activation. Another PP1 inhibitor tautomycetin also has PP1-independent biological actions.…”

Section: Discussionmentioning

confidence: 99%

eIF2α-Independent Inhibition of TNF-α-Triggered NF-κB Activation by Salubrinal

Nakajima

Chi

Gao

et al. 2015

Biological & Pharmaceutical Bulletin

View full text Add to dashboard Cite

Salubrinal is a selective inhibitor of cellular complexes that dephosphorylate eukaryotic translation initiation factor 2α (eIF2α). In previous reports, salubrinal was shown to have the potential to inhibit the activation of nuclear factor-κB (NF-κB) by several stimuli. However, the effects of salubrinal on NF-κB signaling are largely unknown. In this study, we investigated whether and how salubrinal affects NF-κB activation induced by tumor necrosis factor (TNF)-α and interleukin (IL)-1β. We found that salubrinal selectively blocked TNF-α-but not IL-1β-induced activation of NF-κB. This inhibitory effect occurred upstream of transforming growth factor (TGF)-β-activated kinase 1 (TAK1). Further experiments revealed that salubrinal blocked TNF-α-triggered NF-κB activation independent of its action on eIF2α because knockdown of eIF2α by small interfering RNA (siRNA) did not reverse the inhibitory effect of salubrinal on NF-κB. Moreover, guanabenz, a selective inhibitor of the regulatory subunit of protein phosphatase (PP) 1, also preferentially inhibited TNF-α-triggered activation of NF-κB. These findings raise the possibility that salubrinal may selectively block TNF-α-triggered activation of the NF-κB pathway through inhibition of the PP1 complex.Key words salubrinal; nuclear factor-κB; eukaryotic translation initiation factor 2α; protein phosphatase (PP) 1; guanabenz Salubrinal is a small molecule that inhibits the dephosphorylation of eukaryotic translation initiation factor 2α (eIF2α) through the suppression of protein phosphatase (PP) 1 catalytic subunits, resulting in sustained phosphorylation of eIF2α on Ser51. Through this effect, salubrinal protects cells from endoplasmic reticulum (ER) stress-mediated apoptosis.1) It has been shown that salubrinal influences several signaling pathways involved in apoptosis, autophagy and bone homeostasis.2-4) The nuclear factor-κB (NF-κB) pathway is also a target of salubrinal. Recently, Huang et al. reported that salubrinal protected against β-amyloid-triggered neuronal cell death and microglial activation through the suppression of NF-κB activation. 5) Moreover, Hamamura et al. suggested that salubrinal reduced the inflammatory cytokine-driven expression of matrix metalloproteinase 13 via blockade of the p38 mitogen-activated protein kinase pathway and the NF-κB pathway.6) Currently, however, the mechanism by which salubrinal regulates NF-κB remains largely unknown.The Rel/NF-κB family consists of five different members, namely, p50, p52, p65 (RelA), RelB and c-Rel, and functions as a transcription factor through the formation of homo-or heterodimers.7) NF-κB plays crucial roles in the regulation of inflammation, immune responses and apoptosis. 8) In unstimulated cells, NF-κB is retained in the cytoplasm through binding to inhibitors of NF-κB (IκBs). However, in response to several stimuli such as inflammatory cytokines, oxidative stress, ultraviolet light and bacterial components, IκB kinase (IKK) complex including IKKα, IKKβ and IKKγ (also called NF-κB essential modu...

show abstract

Dexmedetomidine inhibits the secretion of high mobility group box 1 from lipopolysaccharide-activated macrophages In vitro

Cited by 46 publications

References 34 publications

Dexmedetomidine Alleviates Hyperoxia-Induced Acute Lung Injury via Inhibiting NLRP3 Inflammasome Activation

Dexmedetomidine Alleviates Hyperoxia-Induced Acute Lung Injury via Inhibiting NLRP3 Inflammasome Activation

RETRACTED: Ketamine reduces lipopolysaccharide-induced high-mobility group box-1 through heme oxygenase-1 and nuclear factor erythroid 2-related factor 2/ p38 mitogen-activated protein kinase

eIF2α-Independent Inhibition of TNF-α-Triggered NF-κB Activation by Salubrinal

Contact Info

Product

Resources

About