scholarly journals Down-regulation of long non-coding RNA SNHG14 protects against acute lung injury induced by lipopolysaccharide through microRNA-34c-3p-dependent inhibition of WISP1

2019 ◽  
Vol 20 (1) ◽  
Author(s):  
Jinyuan Zhu ◽  
Jijia Bai ◽  
Shaojin Wang ◽  
Hui Dong
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Cell Viability ◽  
Quantitative Polymerase Chain Reaction ◽  
Weight Ratio ◽  
Dry Weight ◽  
Luciferase Reporter ◽  
Loss Of Function ◽  
Down Regulation ◽  
Over Expression

Abstract Background Accumulating evidence has shown the important roles of long non-coding RNAs (lncRNAs) in acute lung injury (ALI). This study aimed to investigate the potential role of lncRNA small nucleolar RNA host gene 14 (SNHG14) in lipopolysaccharides (LPS)-induced ALI. Methods Expression of SNHG14, microRNA-34c-3p (miR-34c-3p) and Wnt1 inducible signaling pathway protein 1 (WISP1) in LPS-exposed mouse alveolar macrophages (MH-S) and lung tissues from mice with LPS-induced ALI was determined by reverse transcription quantitative polymerase chain reaction. The interactions among SNHG14, miR-34c-3p and WISP1 were analyzed by dual-luciferase reporter and RIP assays. Using gain-of-function or loss-of-function approaches, the contents of proinflammatory proteins were determined and MH-S cell viability was assessed to evaluate the in vitro functions of SNHG14, miR-34c-3p and WISP1, and wet/dry weight ratio and proinflammatory proteins in lung tissues were determined to assess their in vivo effects. Results SNHG14 and WISP1 expression was increased, while miR-34c-3p was decreased in ALI models. SNHG14 bound to miR-34c-3p, resulting in impaired miR-34c-3p-dependent down-regulation of WISP1. Both SNHG14 silencing and miR-34c-3p over-expression reduced the levels of proinflammatory proteins IL-18, IL-1β, TNF-α and IL-6 and inhibited MH-S cell viability. SNHG14 silencing or miR-34c-3p over-expression decreased the wet/dry weight ratio in lung tissues from ALI mice. The reductions induced by SNHG14 silencing or miR-34c-3p over-expression were rescued by WISP1 over-expression. Conclusion This study demonstrated that lncRNA SNHG14 silencing alleviated inflammation in LPS-induced ALI through miR-34c-3p-mediated inhibition of WISP1. Our findings suggest that lncRNA SNHG14 may serve as a therapeutic target for ALI.

scholarly journals miR-128-3p enhances the protective effect of dexmedetomidine on acute lung injury in septic mice by targeted inhibition of MAPK14

2020 ◽  
Author(s):  
Li Ding ◽  
Xiang Gao ◽  
Shenghui Yu ◽  
Liufang Sheng
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Protective Effect ◽  
Weight Ratio ◽  
Dry Weight ◽  
Expression Level ◽  
Inflammatory Factors ◽  
Luciferase Reporter ◽  
Inflammatory Factor ◽  
Over Expression

Abstract Background: To investigate the mechanism of miR-128-3p and MAPK14 on the protective effect of dexmedetomidine on acute lung injury in septic mice. Methods: SPF C57BL/6 mice were divided into 8 groups. The pathological changes and wet/dry weight ratio (W/D), PaO2, PaCO2, MDA, SOD and MPO levels in lung tissue and the serum levels of inflammation factors were observed. Dual luciferase reporter assay was used to verify the targeting relationship between miR-128-3p and MAPK14. qPCR and WB were used to detect the expression of miR-128-3p and MAPK14. Results: Compared with the Normal group, other groups had lower MDA, MPO, inflammatory factors levels and the expression level of MAPK14, while the content of SOD and the expression level of miR-128-3p was significantly decreased. DEX treatment and up-regulation of miR-128-3p could significantly decrease the contents of MDA, MPO, inflammatory factor levels and significantly increase the SOD content in model mice, however, MAPK14 over-expression had opposite effects. miR-128-3p up-regulation enhanced the changes of above indicators caused by DEX treatment and MAPK14 over-expression could block the protective effect of DEX on acute lung injury in septic mice. miR-128-3p up-regulation reversed the effects of MAPK14 over-expression in model mice. Conclusion: miR-128-3p can further enhance the protective effect of dexmedetomidine on acute lung injury in septic mice by targeting and inhibiting MAPK14 expression.

scholarly journals miR-128-3p enhances the protective effect of dexmedetomidine on acute lung injury in septic mice by targeted inhibition of MAPK14

2020 ◽  
Author(s):  
Li Ding ◽  
Xiang Gao ◽  
Shenghui Yu ◽  
Liufang Sheng
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Protective Effect ◽  
Weight Ratio ◽  
Dry Weight ◽  
Expression Level ◽  
Inflammatory Factors ◽  
Luciferase Reporter ◽  
Inflammatory Factor ◽  
Over Expression

Abstract Background: To investigate the mechanism of miR-128-3p and MAPK14 on the protective effect of dexmedetomidine on acute lung injury in septic mice.Methods: SPF C57BL/6 mice were divided into 8 groups. The pathological changes and wet/dry weight ratio (W/D), PaO2, PaCO2, MDA, SOD and MPO levels in lung tissue and the serum levels of inflammation factors were observed. Dual luciferase reporter assay was used to verify the targeting relationship between miR-128-3p and MAPK14. qPCR and WB were used to detect the expression of miR-128-3p and MAPK14.Results: Compared with the Normal group, other groups had lower MDA, MPO, inflammatory factors levels and the expression level of MAPK14, while the content of SOD and the expression level of miR-128-3p was significantly decreased. DEX treatment and up-regulation of miR-128-3p could significantly decrease the contents of MDA, MPO, inflammatory factor levels and significantly increase the SOD content in model mice, however, MAPK14 over-expression had opposite effects. miR-128-3p up-regulation enhanced the changes of above indicators caused by DEX treatment and MAPK14 over-expression could block the protective effect of DEX on acute lung injury in septic mice. miR-128-3p up-regulation reversed the effects of MAPK14 over-expression in model mice.Conclusion: miR-128-3p can further enhance the protective effect of dexmedetomidine on acute lung injury in septic mice by targeting and inhibiting MAPK14 expression.

scholarly journals miR-128-3p enhances the protective effect of dexmedetomidine on acute lung injury in septic mice by targeted inhibition of MAPK14

2020 ◽  
Author(s):  
Li Ding ◽  
Xiang Gao ◽  
Shenghui Yu ◽  
Liufang Sheng
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Protective Effect ◽  
Weight Ratio ◽  
Dry Weight ◽  
Serum Levels ◽  
Expression Level ◽  
Inflammatory Factors ◽  
Luciferase Reporter ◽  
Targeted Inhibition

Abstract Background: To investigate the role of miR-128-3p and MAPK14 in the dexmedetomidine treatment of acute lung injury in septic mice. Methods: SPF C57BL/6 mice were divided into 8 groups. The pathological changes and wet/dry weight ratio (W/D), PaO 2 , PaCO 2 , MDA, SOD and MPO levels in lung tissue and the serum levels of inflammation factors were observed. Dual luciferase reporter assay was used to detect the targeting relationship of miR-128-3p and MAPK14, and qPCR and WB were used to detect the expression of miR-128-3p and MAPK14. Results: Compared with the Normal group, other groups had lower MDA, MPO, inflammatory factors levels and the expression level of MAPK14, while the content of SOD and the expression level of miR-128-3p was significantly decreased (all p < 0.05). Compared with the Model group, the contents of MDA, MPO, inflammatory factors in the DEX group and miR-128-3p mimic group were significantly decreased, and the content SOD was significantly increased, however, opposite results were occurred in oe-MAPK14 group (all p < 0.05). Compared with the DEX group, all the indicators in miR-128-3p mimic+DEX group showed significant improvement (all p < 0.05). Compared with the miR-128-3p mimic group, all the indicators were deteriorated in the miR-128-3p mimic+oe-MAPK14 group (all p < 0.05). The combination of DEX and oe-MAPK14 blocked the protective effect of dexmedetomidine on acute lung injury in septic mice. Conclusion: miR-128-3p can further enhance the protective effect of dexmedetomidine on acute lung injury in septic mice by targeting and inhibiting MAPK14 expression.

scholarly journals Long non-coding RNA OIP5-AS1 aggravates acute lung injury by promoting inflammation and cell apoptosis via regulating the miR-26a-5p/TLR4 axis

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Qingsong Sun ◽  
Man Luo ◽  
Zhiwei Gao ◽  
Xiang Han ◽  
Weiqin Wu ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Inflammatory Response ◽  
Cell Apoptosis ◽  
Quantitative Polymerase Chain Reaction ◽  
Luciferase Reporter ◽  
Enzyme Linked Immunosorbent Assay ◽  
Interacting Protein ◽  
Wide Range

Abstract Background Acute lung injury (ALI) is a pulmonary disorder that leads to acute respiration failure and thereby results in a high mortality worldwide. Increasing studies have indicated that toll-like receptor 4 (TLR4) is a promoter in ALI, and we aimed to explore the underlying upstream mechanism of TLR4 in ALI. Methods We used lipopolysaccharide (LPS) to induce an acute inflammatory response in vitro model and a murine mouse model. A wide range of experiments including reverse transcription quantitative polymerase chain reaction, western blot, enzyme linked immunosorbent assay, flow cytometry, hematoxylin–eosin staining, RNA immunoprecipitation, luciferase activity and caspase-3 activity detection assays were conducted to figure out the expression status, specific role and potential upstream mechanism of TLR4 in ALI. Result TLR4 expression was upregulated in ALI mice and LPS-treated primary bronchial/tracheal epithelial cells. Moreover, miR-26a-5p was confirmed to target TLR4 according to results of luciferase reporter assay. In addition, miR-26a-5p overexpression decreased the contents of proinflammatory factors and inhibited cell apoptosis, while upregulation of TLR4 reversed these effects of miR-26a-5p mimics, implying that miR-26a-5p alleviated ALI by regulating TLR4. Afterwards, OPA interacting protein 5 antisense RNA 1 (OIP5-AS1) was identified to bind with miR-26a-5p. Functionally, OIP5-AS1 upregulation promoted the inflammation and miR-26a-5p overexpression counteracted the influence of OIP5-AS1 upregulation on cell inflammatory response and apoptosis. Conclusion OIP5-AS1 promotes ALI by regulating the miR-26a-5p/TLR4 axis in ALI mice and LPS-treated cells, which indicates a promising insight into diagnostics and therapeutics in ALI.

scholarly journals Management of Acute Lung Injury: Palmitoylethanolamide as a New Approach

2021 ◽  
Vol 22 (11) ◽  
pp. 5533
Author(s):  
Alessio Filippo Peritore ◽  
Ramona D’Amico ◽  
Rosalba Siracusa ◽  
Marika Cordaro ◽  
Roberta Fusco ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
B Cells ◽  
Lung Injury ◽  
Weight Ratio ◽  
Dry Weight ◽  
Mitogen Activated Protein Kinase ◽  
Histopathological Analysis ◽  
Nuclear Factor ◽  
Intratracheal Administration ◽  
Mitogen Activated Protein

Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are common and devastating clinical disorders with high mortality and no specific therapy. Lipopolysaccharide (LPS) is usually used intratracheally to induce ALI in mice. The aim of this study was to examine the effects of an ultramicronized preparation of palmitoylethanolamide (um-PEA) in mice subjected to LPS-induced ALI. Histopathological analysis reveals that um-PEA reduced alteration in lung after LPS intratracheal administration. Besides, um-PEA decreased wet/dry weight ratio and myeloperoxidase, a marker of neutrophils infiltration, macrophages and total immune cells number and mast cells degranulation in lung. Moreover, um-PEA could also decrease cytokines release of interleukin (IL)-6, interleukin (IL)-1β, tumor necrosis factor (TNF)-α and interleukin (IL)-18. Furthermore, um-PEA significantly inhibited the phosphorylation of nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha (IκBα) and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) activation in ALI, and at the same time decreased extracellular signal-regulated kinase 1/2 (ERK1/2), c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinase (p38/MAPK) expression, that was increased after LPS administration. Our study suggested that um-PEA contrasted LPS-induced ALI, exerting its potential role as an adjuvant anti-inflammatory therapeutic for treating lung injury, maybe also by p38/NF-κB pathway.

Shen-Fu Attenuates Endotoxin-Induced Acute Lung Injury in Rats

2006 ◽  
Vol 34 (04) ◽  
pp. 613-621 ◽  
Author(s):  
Yanning Qian ◽  
Jie Sun ◽  
Zhongyun Wang ◽  
Jianjun Yang
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Pulmonary Inflammation ◽  
Weight Ratio ◽  
Dry Weight ◽  
Nf Kappa B ◽  
Lung Weight ◽  
Tnf Α ◽  
Male Wistar Rats

Sepsis is associated with the highest risk of progression to acute lung injury or acute respiratory distress syndrome. Shen-Fu has been advocated to treat many severely ill patients. Our study was designed to investigate the effect of Shen-Fu on endotoxin-induced acute lung injury in vivo. Adult male Wistar rats were randomly divided into 6 groups: controls; those challenged with endotoxin (5 mg/kg) and treated with saline; those challenged with endotoxin (5 mg/kg) and treated with Shen-Fu (1 mg/kg); those challenged with endotoxin (5 mg/kg) and treated with Shen-Fu (10 mg/kg); increase challenged with endotoxin (5 mg/kg) and treated with Shen-Fu (100 mg/kg); saline injected and treated with Shen-Fu (100 mg/kg). TNF-α, IL-6, and NF-kappa B were investigated in the lung two hours later. Myeloperoxidase (MPO) activity and wet/dry weight ratio were investigated six hours later. Intravenous administration of endotoxin provoked significant lung injury, which was characterized by increment increase of MPO activity and wet/dry lung weight ratio, and TNF-α and IL-6 expression and NF-kappa B activation. Shen-Fu (10,100 mg/kg) decreased MPO activity and wet/dry weight ratio and inhibited TNF-α and IL-6 production, endotoxin-induced NF-kappa B activation. Our results indicated that Shen-Fu at a dose of higher than 10 mg/kg inhibited endotoxin-induced pulmonary inflammation in vivo.

scholarly journals Ganoderic acid A attenuates lipopolysaccharide-induced lung injury in mice

2019 ◽  
Vol 39 (5) ◽  
Author(s):  
Bing Wan ◽  
Yan Li ◽  
Shuangshuang Sun ◽  
Yang Yang ◽  
Yanling LV ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Mouse Model ◽  
Weight Ratio ◽  
Dry Weight ◽  
Lavage Fluid ◽  
Myeloperoxidase Activity ◽  
Protective Effects ◽  
Ganoderic Acid ◽  
Lower Lung

Abstract The present study aimed to investigate the protective effects of ganoderic acid A (GAA) on lipopolysaccharide (LPS)-induced acute lung injury. In mouse model of LPS-induced acute lung injury, we found that GAA led to significantly lower lung wet-to-dry weight ratio and lung myeloperoxidase activity, and attenuated pathological damages. In addition, GAA increased superoxide dismutase activity, but decreased malondialdehyde content and proinflammatory cytokines levels in the bronchoalveolar lavage fluid. Mechanistically, GAA reduced the activation of Rho/ROCK/NF-κB pathway to inhibit LPS-induced inflammation. In conclusion, our study suggests that GAA attenuates acute lung injury in mouse model via the inhibition of Rho/ROCK/NF-κB pathway.

scholarly journals Anti-Inflammatory Effects of Monoammonium Glycyrrhizinate on Lipopolysaccharide-Induced Acute Lung Injury in Mice through Regulating Nuclear Factor-Kappa B Signaling Pathway

2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Xiaoying Huang ◽  
Jiangfeng Tang ◽  
Hui Cai ◽  
Yi Pan ◽  
Yicheng He ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Signaling Pathway ◽  
Interleukin 1 ◽  
Intratracheal Instillation ◽  
Weight Ratio ◽  
Dry Weight ◽  
Inflammatory Cells ◽  
Lavage Fluid ◽  
Therapeutic Mechanism

The present study aimed to investigate the therapeutic effect of monoammonium glycyrrhizinate (MAG) on lipopolysaccharide- (LPS-) induced acute lung injury (ALI) in mice and possible mechanism. Acute lung injury was induced in BALB/c mice by intratracheal instillation of LPS, and MAG was injected intraperitoneally 1 h prior to LPS administration. After ALI, the histopathology of lungs, lung wet/dry weight ratio, protein concentration, and inflammatory cells in the bronchoalveolar lavage fluid (BALF) were determined. The levels of tumor necrosis factor-α(TNF-α) and interleukin-1β(IL-1β) in the BALF were measured by ELISA. The activation of NF-κB p65 and IκB-αof lung homogenate was detected by Western blot. Pretreatment with MAG attenuated lung histopathological damage induced by LPS and decreased lung wet/dry weight ratio and the concentrations of protein in BALF. At the same time, MAG reduced the number of inflammatory cells in lung and inhibited the production of TNF-αand IL-1βin BALF. Furthermore, we demonstrated that MAG suppressed activation of NF-κB signaling pathway induced by LPS in lung. The results suggested that the therapeutic mechanism of MAG on ALI may be attributed to the inhibition of NF-κB signaling pathway. Monoammonium glycyrrhizinate may be a potential therapeutic reagent for ALI.

scholarly journals Tanshinone IIA ameliorates acute lung injury by inhibition of the NLRP3 inflammasome

2019 ◽  
Vol 71 (2) ◽  
pp. 315-320 ◽  
Author(s):  
Tianyu Chen ◽  
Shaoyun Qin ◽  
Ying Dai
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Partial Pressure ◽  
Nlrp3 Inflammasome ◽  
Weight Ratio ◽  
Dry Weight ◽  
Tanshinone Iia ◽  
Inflammasome Activation ◽  
Co2 Partial Pressure ◽  
O2 Partial Pressure

Tanshinone IIA is the phenanthrenequinone derivative extracted from the perennial plant Salvia miltiorrhiza Bunge (red sage). We investigated whether inhibition of the nucleotide-binding oligomerization domain (NOD)-like receptor family protein 3 (NLRP3) inflammasome mediates the protective effect of tanshinone IIA in acute lung injury (ALI) induced in rats by oleic acid (OA) injection. Compared with the control treatment, OA injection induced pulmonary histological impairment, increased the lung wet/dry weight ratio (7.0?1.1 vs 4.?0.6 ) and CO2 partial pressure (PaCO2) (52?6.4 vs 40?3.6 mmHg), decreased arterial O2 partial pressure (PaO2) (63?8.4 vs 100?3.0 mmHg), and increased tumor necrosis factor ? (TNF?) (8.8?2.3 vs 5.2 ?1.5 pg/mL), monocyte chemoattractant protein-1 (MCP-1) (36.1?4.9 vs 25.2?6.6 pg/mL) and interleukin-1? (IL-1?) (15.9?3.2 vs 4.6?1.3 pg/mL) in the bronchoalveolar lavage (BAL) fluid. Tanshinone IIA provided protection against ALI, observed as a reduction in the lung wet/dry weight ratio and CO2 partial pressure, and increased O2 partial pressure. The cytokine increase was also prevented. Tanshinone IIA attenuated increased protein levels of NLRP3, caspase-1 and IL-1? in pulmonary tissues, suggesting that it ameliorates ALI by preventing NLRP3 inflammasome activation.

scholarly journals Down-regulation of miR-let-7e attenuates LPS-induced acute lung injury in mice via inhibiting pulmonary inflammation by targeting SCOS1/NF-κB pathway

2021 ◽  
Vol 41 (1) ◽  
Author(s):  
Wuquan Li ◽  
Wentao Zhang ◽  
Jun Liu ◽  
Yalong Han ◽  
He Jiang ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Inflammatory Response ◽  
Inflammatory Diseases ◽  
Pulmonary Inflammation ◽  
Lavage Fluid ◽  
Luciferase Reporter ◽  
Cytokine Signaling ◽  
Down Regulation ◽  
Reporter Assays

Abstract Excessive pulmonary inflammatory response is critical in the development of acute lung injury (ALI). Previously, microRNAs (miRNAs) have been recognized as an important regulator of inflammation in various diseases. However, the effects and mechanisms of miRNAs on inflammatory response in ALI remain unclear. Herein, we tried to screen miRNAs in the processes of ALI and elucidate the potential mechanism. Using a microarray assay, microRNA let-7e (let-7e) was chose as our target for its reported suppressive roles in several inflammatory diseases. Down-regulation of let-7e by antagomiR-let-7e injection attenuated LPS-induced acute lung injury. We also found that antagomiR-let-7e could obviously improve the survival rate in ALI mice. Moreover, antagomiR-let-7e treatment reduced the production of proinflammatory cytokines (i.e., TNF-α, IL-1β and IL-6) in bronchoalveolar lavage fluid (BALF) of LPS-induced ALI mice. Luciferase reporter assays confirmed that suppressor of cytokine signaling 1 (SOCS1), a powerful attenuator of nuclear factor kappa B (NF-κB) signaling pathway, was directly targeted and suppressed by let-7e in RAW264.7 cells. In addition, it was further observed that SOCS1 was down-regulated, and inversely correlated with let-7e expression levels in lung tissues of ALI mice. Finally, down-regulation of let-7e suppressed the activation of NF-κB pathway, as evidenced by the reduction of p-IκBα, and nuclear p-p65 expressions in ALI mice. Collectively, our findings indicate that let-7e antagomir protects mice against LPS-induced lung injury via repressing the pulmonary inflammation though regulation of SOCS1/NF-κB pathway, and let-7e may act as a potential therapeutic target for ALI.

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