Dexmedetomidine alleviates lung injury in sepsis mice through regulating P38 MAPK signaling pathway

Shao, Yanmei; Chen, Xia; Liu, Yaoqi; Chen, Xiaoxue; Li, Cuiping; Wang, Lili; Zhao, Wanjun

doi:10.23736/s0031-0808.20.03885-9

Cited by 5 publications

(6 citation statements)

References 4 publications

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“…Therefore, dampening the interaction between Nur77 and p38α would favor Nur77 suppression of the hyperinflammatory response 16 . Growing evidence has suggested that Dex alleviates lung intestinal ischemia–reperfusion injury and neurogenesis damage in sepsis mice through regulating the P38 MAPK signaling pathway 41,42 . Therefore, we investigated whether Dex would affect inflammatory factors and organ injury by regulating Nur77 to further clarify the anti‐inflammatory mechanism of Dex.…”

Section: Discussionmentioning

confidence: 99%

“…16 Growing evidence has suggested that Dex alleviates lung intestinal ischemia-reperfusion injury and neurogenesis damage in sepsis mice through regulating the P38 MAPK signaling pathway. 41,42 Therefore, we investigated whether Dex would affect inflammatory factors We successfully established an inflammatory model using LPS-treated RAW264.7 cells. Treatment with LPS induced the upregulation of Nur77, and Dex could further increase the expression of Nur77.…”

Section: Discussionmentioning

confidence: 99%

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Dexmedetomidine attenuates inflammation and organ injury partially by upregulating Nur77 in sepsis

Zhang

Huang

Gong

et al. 2023

Immunity Inflam & Disease

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The aim of this study was to investigate the effect of dexmedetomidine (Dex) on inflammation and organ injury in sepsis, as well as the potential relationship between Dex and nuclear receptor 77 (Nur77). Methods:We investigated the effects of dexmedetomidine on lipopolysaccharide (LPS)-induced inflammation in RAW264.7 cells and organ injury in the cecal ligation and puncture (CLP) mouse model. Additionally, we examined the relationship between dexmedetomidine and Nur77. The expression levels of Nur77 in RAW264.7 cells were analyzed under various types of stimulation using quantitative reverse transcription polymerase chain reaction and western blot analysis. Inflammatory cytokine levels in the cells were evaluated using enzyme-linked immunoassay. Organ injuries were assessed by examining tissue histology and pathology of the lung, liver, and kidney. Results: Dexmedetomidine increased the expression of Nur77 and IL-10, and downregulated inflammatory cytokines (IL-1β and TNF-α) in LPS-treated RAW264.7 cells. The effect of dexmedetomidine on inhibiting inflammation in LPS-treated RAW264.7 cells was promoted by overexpressing Nur77, while it was reversed by downregulating Nur77. Additionally, dexmedetomidine promoted the expression of Nur77 in the lung and CLP-induced pathological changes in the lung, liver, and kidney. Activation of Nur77 with the agonist Cytosporone B (CsnB) significantly suppressed the production of IL-1β and TNF-α in LPS-treated RAW264.7 cells. In contrast, knockdown of Nur77 augmented IL-1β and TNF-α production in LPS-treated RAW264.7 cells.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Dexmedetomidine attenuates inflammation and organ injury partially by upregulating Nur77 in sepsis

Zhang

Huang

Gong

et al. 2023

Immunity Inflam & Disease

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“…Moreover, ZEB1 overexpression was capable of reversing the protective roles of miR-374a-5p in LPS-induced cell injury of HPMVECs. Extensive evidence indicates that aberrant activation of the p38 MAPK signaling pathway contributes to the pathogenesis of sepsis-induced ALI (24)(25)(26). In addition, ZEB1 is increased in LPS-induced pulmonary fibrosis, which is associated with the p38 MAPK signaling pathway (27).…”

Section: Discussionmentioning

confidence: 99%

“…It has been reported that ZEB1 induces inflammatory response in periodontal disease and liver fibrosis (22,23). In addition, the p38 MAPK signaling pathway is associated with septic lung injury (24)(25)(26). A previous study revealed that the p38 MAPK pathway could be restricted by miR-200s by targeting ZEB1/2 in LPS-induced pulmonary fibrosis (27).…”

Section: Mir-374a-5p Alleviates Sepsis-induced Acute Lung Injury By T...mentioning

confidence: 99%

miR‑374a‑5p alleviates sepsis‑induced acute lung injury by targeting ZEB1 via the p38 MAPK pathway

Shen

2022

Exp Ther Med

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The aim of the present study was to investigate the effects of microRNA (miR)-374a-5p on sepsis-induced acute lung injury (ALI) and the associated mechanism. Lipopolysaccharide (LPS)-induced human pulmonary microvascular endothelial cells (HPMVECs) were used to construct the cellular model of sepsis. A luciferase reporter assay was performed to confirm the association between miR-374a-5p and zinc finger E-box binding homeobox 1 (ZEB1). Reverse transcription-quantitative polymerase chain reaction and western blot analysis were performed to assess the relative expression of miR-374a-5p, ZEB1 and apoptosis-related proteins. Cell viability and apoptosis were determined by Cell Counting Kit-8 assay and flow cytometry, respectively. Enzyme-linked immunosorbent assays were used to evaluate inflammatory cytokines. The results revealed that miR-374a-5p was downregulated in sepsis patients and LPS-treated HPMVECs. Upregulation of miR-374a-5p alleviated LPS-triggered cell injury in HPMVECs, as evidenced by restoration of cell viability, and inhibition of apoptosis and the production of proinflammatory cytokines. In addition, ZEB1 was revealed to be a downstream target of miR-374a-5p, and overexpression of ZEB1 could reverse the anti-apoptotic and anti-inflammatory effects of miR-374a-5p on an LPS-induced sepsis cell model. Moreover, miR-374a-5p-induced protective effects involved the p38 MAPK signaling pathway. Collectively, miR-374a-5p exerted a protective role in sepsis-induced ALI by regulating the ZEB1-mediated p38 MAPK signaling pathway, providing a potential target for the diagnosis and treatment of sepsis.

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“…The mitogen-activated protein kinase (MAPK) pathway is activated downstream of TLR4. MAPKs, including extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and p38 kinase, play crucial roles in the production of proinflammatory cytokines and the regulation of immune cell activation [16,17]. Moreover, the interferon regulatory factor 3 (IRF3) pathway contributes to the production of type I interferons and other proinflammatory cytokines [18].…”

Section: Inflammatory Pathways In Sepsismentioning

confidence: 99%

Unlocking the Potential: Quercetin and Its Natural Derivatives as Promising Therapeutics for Sepsis

Wang,

Lv,

Feng

et al. 2024

Biomedicines

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Sepsis is a syndrome of organ dysfunction caused by an uncontrolled inflammatory response, which can seriously endanger life. Currently, there is still a shortage of specific therapeutic drugs. Quercetin and its natural derivatives have received a lot of attention recently for their potential in treating sepsis. Here, we provide a comprehensive summary of the recent research progress on quercetin and its derivatives, with a focus on their specific mechanisms of antioxidation and anti-inflammation. To obtain the necessary information, we conducted a search in the PubMed, Web of Science, EBSCO, and Cochrane library databases using the keywords sepsis, anti-inflammatory, antioxidant, anti-infection, quercetin, and its natural derivatives to identify relevant research from 6315 articles published in the last five years. At present, quercetin and its 11 derivatives have been intensively studied. They primarily exert their antioxidation and anti-inflammation effects through the PI3K/AKT/NF-κB, Nrf2/ARE, and MAPK pathways. The feasibility of these compounds in experimental models and clinical application were also discussed. In conclusion, quercetin and its natural derivatives have good application potential in the treatment of sepsis.

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Dexmedetomidine alleviates lung injury in sepsis mice through regulating P38 MAPK signaling pathway

Cited by 5 publications

References 4 publications

Dexmedetomidine attenuates inflammation and organ injury partially by upregulating Nur77 in sepsis

Dexmedetomidine attenuates inflammation and organ injury partially by upregulating Nur77 in sepsis

miR‑374a‑5p alleviates sepsis‑induced acute lung injury by targeting ZEB1 via the p38 MAPK pathway

Unlocking the Potential: Quercetin and Its Natural Derivatives as Promising Therapeutics for Sepsis

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