Piper Kadsura Extract Inhibits miR-155 to Protect Lipopolysaccharide-Induced Acute Lung Injury

2021 ◽  
Vol 11 (10) ◽  
pp. 2010-2016
Author(s):  
Xiufeng Li ◽  
Yingna Li ◽  
Qinmei Zhang
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Inflammatory Responses ◽  
Protective Role ◽  
Inflammatory Factors ◽  
High Dose ◽  
Inflammatory Infiltration ◽  
Butanol Extract ◽  
Induced Apoptosis ◽  
Effective Drugs

Acute lung injury (ALI) is a common and critical disease encountered in clinical practice. When the disease progresses to a more serious stage, it is called acute respiratory distress syndrome and is associated with a high mortality rate. However, there is a lack of specific drugs for treating this disease; therefore, it is very important to find safe and effective drugs for treatment. Piper kadsura (P. kadsura), part of the of the vin family Piperaceae, has a capability to dispel wind and dampness and its n-butanol extract can provide protection against inflammatory responses, such as inflammatory infiltration and hyperplasia of synovial tissue of joints. In order to explore the therapeutic effect of P. kadsura extract on ALI, we treated HPAEpiC cells with different doses of its extract. We found that after treatment using low-medium and high-dose P. kadsura extract, the optical density value was decreased in HPAEpiC cells as induced by lipopolysaccharide (LPS). In addition, the following were statistically and significantly decreased in a dose-dependent (P < 0.05): the apoptosis rate, cleaved-caspase3 expression, the expression levels of TNF-α, IL-6, and miR-155. However, procaspase 3 increased the expression of miR-155, which can promote LPS-induced apoptosis and the release of inflammatory factors in HPAEpiC cells. The overexpressed miR-155 can weaken the protection conferred by P. kadsura extract on ALI. These results suggest that P. kadsura extract may play a protective role against ALI induced by LPS by decreasing the expression of miR-155.

scholarly journals Ghrelin attenuates sepsis-induced acute lung injury by inhibiting the NF-κB, iNOS, and Akt signaling in alveolar macrophages

2019 ◽  
Vol 317 (3) ◽  
pp. L381-L391 ◽  
Author(s):  
Haichong Zheng ◽  
Wenjie Liang ◽  
Wanmei He ◽  
Chunrong Huang ◽  
Qingui Chen ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Alveolar Macrophages ◽  
Inflammatory Responses ◽  
Pulmonary Inflammation ◽  
Cecal Ligation ◽  
Protective Role ◽  
Akt Signaling ◽  
Cytokines And Chemokines

Ghrelin has proven to be protective against sepsis-induced acute lung injury (ALI) via anti-inflammatory effects. However, its mechanisms remain poorly understood. Alveolar macrophages (AMs) play a key role in mediating inflammatory responses during sepsis-induced ALI by secretion of cytokines and chemokines. This study was undertaken to investigate whether ghrelin suppresses inflammatory effects of AMs and therefore may help to attenuate sepsis-induced ALI. A sepsis model in rats was achieved using cecal ligation and puncture. Ghrelin treatment markedly improved histopathological changes in the lungs and reduced pulmonary inflammation in septic rats. NF-κB translocation and p-Akt and inducible nitric oxide synthase (iNOS) activities in AMs from septic rats were suppressed by ghrelin. In vitro data indicated that ghrelin decreased the levels of LPS-induced IL-1β, TNF-α, and IL-6, NF-κB translocation, and iNOS and Akt activities of AMs. Furthermore, the NF-κB/iNOS pathway or Akt signaling was positively correlated with LPS-induced inflammatory production of AMs in vitro. In conclusion, ghrelin exerts a protective role against sepsis-induced ALI probably by reducing the production of inflammatory cytokines from AMs via inhibition of the NF-κB/iNOS pathway or Akt signaling.

scholarly journals LncRNA SNHG1 suppresses LPS-induced acute lung injury by regulating miR-421/TIMP3 axis

2021 ◽  
Author(s):  
Zeyu Jiang ◽  
Jinyi Tan ◽  
Yan Yuan ◽  
Jiang Shen ◽  
Yan Chen
Keyword(s):  
Flow Cytometry ◽  
Acute Lung Injury ◽  
Lung Injury ◽  
Inflammatory Responses ◽  
A549 Cells ◽  
Luciferase Reporter ◽  
Elisa Assay ◽  
Tnf Α ◽  
Non Coding Rnas ◽  
Induced Apoptosis

AbstractExtensive evidence has revealed the crucial roles of long non-coding RNAs (lncRNAs) in acute lung injury (ALI). This study aimed to explore the mechanism of lncRNA SNHG1 in lipopolysaccharides (LPS)-induced ALI. RT-qPCR was employed to test the levels of SNHG1, miR-421 and TIMP3 in A549 cells. Cell viability and apoptosis were assessed by CCK-8 assay and flow cytometry. ELISA assay was adopted to examine the levels of inflammatory-related cytokines, including IL-1β, IL-6 and TNF-α. The binding sequences of miR-421 and SNHG1 or TIMP3 were predicted using starBase software. Then dual-luciferase reporter and RIP assays were adopted to verify the interaction between miR-421 and SNHG1 or TIMP3. The protein level of TIMP3 was measured by western blotting. It was found that LPS stimulation downregulated SNHG1 level and SNHG1 addition decreased viability, and induced apoptosis as well as promoted inflammatory responses in LPS-treated A549 cells. SNHG1 could sponge miR-421 and SNHG1 protected A549 cells from LPS-induced injury via inhibiting miR-421. Moreover, TIMP3 was a target of miR-421. MiR-421 silence protected A549 cells against the LPS-triggered inhibition in viability, and promotion in apoptosis and inflammatory responses. SNHG1 could upregulate TIMP3 through acting as a ceRNA of miR-421 in A549 cells. Altogether, the present study elaborated that SNHG1 inhibited LPS-stimulated ALI by modulating the miR-421/TIMP3 axis.

scholarly journals Serinc2 deficiency causes susceptibility to sepsis-associated acute lung injury

2021 ◽  
Author(s):  
Shuai Mao ◽  
Jian Lv ◽  
Meng Chen ◽  
Ningning Guo ◽  
Yu Fang ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Inflammatory Responses ◽  
Cecal Ligation ◽  
Underlying Mechanism ◽  
Raw264.7 Cells ◽  
Inflammatory Factors ◽  
High Morbidity ◽  
Positive Staining ◽  
Protective Effects

Abstract Background Severe sepsis and its subsequent complications cause high morbidity and mortality rates worldwide. Lung is one of the most vulnerable organs sensitive to sepsis-associated inflammatory storm, and usually develops into acute respiratory distress syndrome (ARDS)/acute lung injury (ALI). The pathogenesis of sepsis-associated ALI is accompanied by coordinated transmembrane signal transduction and subsequent programmed cell death; however, the underlying mechanism remains largely unclear. Results Here we find that the expression of serine incorporator 2 (Serinc2), a protein involved in phosphatidylserine synthesis and membrane incorporation, is upregulated in cecal ligation and puncture (CLP)-induced ALI. Furthermore, serinc2-knockout (KO) mouse line is generated by CRISPR-cas9 approach. Compared with wildtype mice, the Serinc2-KO mice exhibit exacerbated ALI-related pathologies after CLP. The expressions of pro-inflammatory factors, including IL1β, IL6, TNFα, and MCP1, are significantly enhanced by Serinc2 deficiency, concurrent with over-activation of STAT3, p38 and ERK pathways. Conversely, Serinc2 overexpression in RAW264.7 cells significantly suppresses the inflammatory responses induced by lipopolysaccharide (LPS). Serinc2 KO aggravates CLP-induced apoptosis as evidenced by increases in TUNEL-positive staining, Bax expression, and Caspase-3 cleavage and decreases in BCL-2 expression and Akt phosphorylation, whereas these changes are suppressed by Serinc2 overexpression in LPS-treated RAW264.7 cells. Moreover, administration of AKTin, an inhibitor of Akt, abolishes the protective effects of Serinc2 overexpression against inflammation and apoptosis. Conclusions Our findings demonstrate a protective role of Serinc2 in the lung through activating the Akt pathway, and provide novel insight into the pathogenesis of sepsis-induced ALI.

High-dose heparin fails to improve acute lung injury following smoke inhalation in sheep

2003 ◽  
Vol 104 (4) ◽  
pp. 349-356 ◽  
Author(s):  
Kazunori MURAKAMI ◽  
Perenlei ENKHBAATAR ◽  
Katsumi SHIMODA ◽  
Akio MIZUTANI ◽  
Robert A. COX ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Inflammatory Responses ◽  
Inhalation Injury ◽  
Smoke Inhalation ◽  
High Dose ◽  
Heparin Infusion ◽  
Infusion Group ◽  
Dose Heparin ◽  
Lung Dysfunction

Thrombin is involved in various inflammatory responses. In sepsis, coagulation abnormalities are major complications. Acute lung injury is one of the most life-threatening problems that can result from sepsis. We hypothesized that high-dose heparin might be effective in attenuating acute lung injury in our sepsis model. Female sheep (n = 16) were surgically prepared for the study. After a tracheotomy, 48 breaths of cotton smoke (<40°C) were insufflated into the airway. Afterwards, live Pseudomonas aeruginosa (5×1011 colony-forming units) bacteria were instilled into the lung. All sheep were ventilated mechanically with 100% O2, and were divided into three groups: a heparin infusion group (n = 6), a Ringer's lactate infusion group (n = 6), and a sham-injury group (n = 4; surgically prepared in the same fashion but receiving no inhalation injury or bacteria). The treatment was started 1h after the insult, and was continued thereafter for 24h. The dose of heparin was adjusted by monitoring to target an activated clotting time of between 300 and 400s (baseline = approx. 150s). Sheep exposed to lung injury presented with typical hyperdynamic cardiovascular changes, including an increased cardiac output and a fall in systemic vascular resistance. There was a decrease in the arterial partial pressure of O2. In conclusion, high-dose heparin did not prevent lung dysfunction in this model, in which acute lung injury was induced by combined smoke and septic challenge.

scholarly journals Map kinase phosphatase 5 protects against sepsis-induced acute lung injury

2012 ◽  
Vol 302 (9) ◽  
pp. L866-L874 ◽  
Author(s):  
Feng Qian ◽  
Jing Deng ◽  
Benjamin N. Gantner ◽  
Richard A. Flavell ◽  
Chen Dong ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Inflammatory Responses ◽  
Critical Role ◽  
Inflammatory Cells ◽  
Neutrophil Infiltration ◽  
Inflammatory Factors ◽  
Lps Challenge ◽  
Map Kinase Phosphatase ◽  
Severe Lung

Mitogen-activated protein kinases (MAPKs) play a critical role in inflammation. Although activation of MAPK in inflammatory cells has been studied extensively, much less is known about the inactivation of these kinases. MAPK phosphatase 5 (MKP5) is a member of the dual-specificity phosphatase family that dephosphorylates activated MAPKs. Here we report that MKP5 protects sepsis-induced acute lung injury. Mice lacking MKP5 displayed severe lung tissue damage following LPS challenge, characterized with increased neutrophil infiltration and edema compared with wild-type (WT) controls. In response to LPS, MKP5-deficient macrophages produced significantly more inflammatory factors including inflammatory cytokines, nitric oxide, and superoxide. Phosphorylation of p38 MAPK, JNK, and ERK were enhanced in MKP5-deficient macrophages upon LPS stimulation. Adoptive transfer of MKP5-deficient macrophages led to more severe lung inflammation than transfer of WT macrophages, suggesting that MKP5-deficient macrophages directly contribute to acute lung injury. Taken together, these results suggest that MKP5 is crucial to homeostatic regulation of MAPK activation in inflammatory responses.

Chelidonine Attenuates Sepsis-Induced Acute Lung Injury via Suppressing Toll-like Receptor 4/Myeloid Differentiation Factor 88/Nuclear Factor-॔B Signaling Pathway in Newborn Mice

2020 ◽  
Vol 19 (1) ◽  
pp. 120-126
Author(s):  
Ayinuerguli Adili ◽  
Adilijiang Kari ◽  
Chuanlong Song ◽  
Abulaiti Abuduhaer
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Nuclear Factor Kappa B ◽  
Myeloid Differentiation ◽  
Nuclear Factor ◽  
Toll Like Receptor ◽  
Toll Like Receptor 4 ◽  
Inflammatory Infiltration ◽  
Newborn Mice ◽  
Myeloid Differentiation Factor

We have examined the mechanism underlying amelioration of sepsis-induced acute lung injury by chelidonine in newborn mice. To this end, a sepsis model was established using cecal ligation and puncture in newborn mice. The sepsis-induced acute lung injury was associated with an increased inflammatory infiltration and pulmonary congestion, as well as abnormal alveolar morphology. The lung injury-associated increased tumor necrosis factor-α and interleukin-1β in bronchoalveolar lavage fluid and lung, the markers of inflammatory infiltration and pulmonary congestion, diminished by chelidonine treatment. Chelidonine administration also downregulated protein levels of toll-like receptor 4, myeloid differentiation factor 88, phosphorylated nuclear factor-kappa B, and nuclear factor-kappa B that are elevated in response to sepsis. In conclusion, chelidonine provides a potential therapeutic strategy for newborn mice with acute lung injury.

scholarly journals In vitro and in vivo assessment of the protective effect of sufentanil in acute lung injury

2021 ◽  
Vol 49 (2) ◽  
pp. 030006052098635
Author(s):  
Qi Gao ◽  
Ningqing Chang ◽  
Donglian Liu
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Protective Effect ◽  
High Mobility ◽  
Terminal Deoxynucleotidyl Transferase ◽  
Inflammatory Factors ◽  
Luciferase Reporter ◽  
Hmgb1 Protein

Objectives To investigate the mechanisms underlying the protective effect of sufentanil against acute lung injury (ALI). Material and Methods Rats were administered lipopolysaccharide (LPS) by endotracheal instillation to establish a model of ALI. LPS was used to stimulate BEAS-2B cells. The targets and promoter activities of IκB were assessed using a luciferase reporter assay. Apoptosis of BEAS-2B cells was evaluated by terminal deoxynucleotidyl transferase dUTP nick end labeling. Results Sufentanil treatment markedly reduced pathological changes in lung tissue, pulmonary edema and secretion of inflammatory factors associated with ALI in vivo and in vitro. In addition, sufentanil suppressed apoptosis induced by LPS and activated NF-κB both in vivo and in vitro. Furthermore, upregulation of high mobility group box protein 1 (HMGB1) protein levels and downregulation of miR-129-5p levels were observed in vivo and in vitro following sufentanil treatment. miR-129-5p targeted the 3ʹ untranslated region and its inhibition decreased promoter activities of IκB-α. miR-129-5p inhibition significantly weakened the protective effect of sufentanil on LPS-treated BEAS-2B cells. Conclusion Sufentanil regulated the miR-129-5p/HMGB1 axis to enhance IκB-α expression, suggesting that sufentanil represents a candidate drug for ALI protection and providing avenues for clinical treatment.

scholarly journals Plasma extracellular vesicle delivery of miR-210-3p by targeting ATG7 to promote sepsis-induced acute lung injury by regulating autophagy and activating inflammation

2021 ◽  
Author(s):  
Guang Li ◽  
Bo Wang ◽  
Xiangchao Ding ◽  
Xinghua Zhang ◽  
Jian Tang ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Recipient Cell ◽  
Cecal Ligation ◽  
Cell Permeability ◽  
Cell Counting ◽  
Inflammatory Factors ◽  
Luciferase Reporter ◽  
Enzyme Linked Immunosorbent Assay ◽  
Vascular Density

AbstractExtracellular vesicles (EVs) can be used for intercellular communication by facilitating the transfer of miRNAs from one cell to a recipient cell. MicroRNA (miR)-210-3p is released into the blood during sepsis, inducing cytokine production and promoting leukocyte migration. Thus, the current study aimed to elucidate the role of plasma EVs in delivering miR-210-3p in sepsis-induced acute lung injury (ALI). Plasma EVs were isolated from septic patients, after which the expression of various inflammatory factors was measured using enzyme-linked immunosorbent assay. Cell viability and apoptosis were measured via cell counting kit-8 and flow cytometry. Transendothelial resistance and fluorescein isothiocyanate fluorescence were used to measure endothelial cell permeability. Matrigel was used to examine the tubulogenesis of endothelial cells. The targeting relationship between miR-210-3p and ATG7 was assessed by dual-luciferase reporter assays. The expression of ATG7 and autophagy-related genes was determined to examine autophagic activation. A sepsis mouse model was established by cecal ligation and puncture (CLP)-induced surgery. The level of miR-210-3p was highly enriched in septic EVs. MiR-210-3p enhanced THP-1 macrophage inflammation, BEAS-2B cell apoptosis, and HLMVEC permeability while inhibiting angiogenesis and cellular activity. MiR-210-3p overexpression reduced ATG7 and LC3II/LC3I expression and increased P62 expression. Improvements in vascular density and autophagosome formation, increased ATG7 expression, and changes in the ratio of LC3II/LC3I were detected, as well as reduced P62 expression, in adenovirus-anti-miR-210-3p treated mice after CLP injury. Taken together, the key findings of the current study demonstrate that plasma EVs carrying miR-210-3p target ATG7 to regulate autophagy and inflammatory activation in a sepsis-induced ALI model.

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