Pharmacological Effects of Marine-Derived Enterococcus faecium EA9 against Acute Lung Injury and Inflammation in Cecal Ligated and Punctured Septic Rats

Microorganisms obtained from the marine environment may represent a potential therapeutic value for multiple diseases. This study explored the possible protective role of marine-derived potential probiotic Enterococcus faecium EA9 (E. faecium) against pulmonary inflammation and oxidative stress using the cecal ligation and puncture (CLP) model of sepsis in Wistar rats. Animals were pretreated with E. faecium for 10 days before either sham or CLP surgeries. Animals were sacrificed 72 hours following the surgical intervention. The histological architecture of lung tissues was evaluated as indicated by the lung injury score. In addition, the extend of pulmonary edema was determined as wet/dry weight ratio. The inflammatory cytokines were estimated in lung tissues, including tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and interleukin-1 beta (IL-1β) using the enzyme-linked-immunosorbent-assay (ELISA) technique. Moreover, markers for lipid peroxidation such as thiobarbituric acid reaction substances (TBARs), and endogenous antioxidants, including reduced glutathione (GSH) were determined in lung tissues. Finally, the enzymatic activities of antioxidant enzymes such as catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx), and glutathione reductase (GR) were assayed in the lungs. Pretreatment with E. faecium markedly attenuated CLP-induced lung injury and pulmonary edema. Markers for inflammation, including TNF-α, IL-6, and IL-1β were augmented in the lung tissues of CLP animals, while E. faecium ameliorated their augmented levels. E. faecium pretreatment also restored the elevated TBARS levels and the prohibited CAT, SOD, and GPx enzymatic activities in CLP animals. GSH levels were corrected by E. faecium in CLP animals. The inflammatory and lipid peroxidation mediators were positively correlated, while antioxidant enzymatic activities were negatively correlated with CLP-induced lung injury and pulmonary edema. Collectively, marine-derived Enterococcus faecium EA9 might be considered as a prospective therapeutic tool for the management of pulmonary dysfunction associated with sepsis.

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Angelica Polysaccharide Ameliorates Sepsis-Induced Acute Lung Injury through Inhibiting NLRP3 and NF-κB Signaling Pathways in Mice

Mediators of Inflammation ◽

10.1155/2021/8866143 ◽

2021 ◽

Vol 2021 ◽

pp. 1-9

Author(s):

Yan Zhu ◽

Taocheng Meng ◽

Aichen Sun ◽

Jintao Li ◽

Jinlai Li

Keyword(s):

Acute Lung Injury ◽

Lung Injury ◽

Signaling Pathways ◽

Cecal Ligation ◽

Weight Ratio ◽

Receptor Protein ◽

Lung Edema ◽

Caspase 1 ◽

Tnf Α

Objective. This study aimed to explore the role of angelica polysaccharide (AP) in sepsis-induced acute lung injury (ALI) and its underlying molecular mechanism. Methods. A sepsis model of cecal ligation and puncture (CLP) in male BALB/C mice was used. Then, 24 h after CLP, histopathological changes in lung tissue, lung wet/dry weight ratio, and inflammatory cell infiltration were analyzed. Next, levels of inflammatory cytokines (tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, IL-6, and IL-18), as well as the activity of myeloperoxidase (MPO), malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione (GSH), were measured to assess the role of AP. The protein expression of NF-κB p65, p-NF-κB p65, IκBα, p-IκBα, nucleotide-binding domain- (NOD-) like receptor protein 3 (NLRP3), ASC, and caspase-1 was detected by western blot. In addition, the expression of p-NF-κB p65 and NLRP3 was detected by immunohistochemistry. Results. AP treatment ameliorated CLP-induced lung injury and lung edema, as well as decreased the number of total cells, neutrophils, and macrophages in bronchoalveolar lavage fluid (BALF). AP reduced the levels of TNF-α, IL-1β, IL-6, and IL-18 in BALF, as well as in serum. Moreover, AP decreased MPO activity and MDA content, whereas increased SOD and GSH levels. AP inhibited the expression of p-NF-κB p65, p-IκBα, NLRP3, ASC, and caspase-1, while promoted IκBα expression. Conclusion. This study demonstrated that AP exhibits protective effects against sepsis-induced ALI by inhibiting NLRP3 and NF-κB signaling pathways in mice.

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Exosomes from adipose-derived mesenchymal stem cells alleviate sepsis-induced lung injury in mice by inhibiting the secretion of IL-27 in macrophages

Cell Death Discovery ◽

10.1038/s41420-021-00785-6 ◽

2022 ◽

Vol 8 (1) ◽

Author(s):

Xiaoyan Wang ◽

Danyong Liu ◽

XiHe Zhang ◽

LiuMing Yang ◽

Zhengyuan Xia ◽

...

Keyword(s):

Lung Injury ◽

Pulmonary Edema ◽

Tissue Injury ◽

Cecal Ligation ◽

Wild Type Mouse ◽

Vascular Leakage ◽

Inflammatory Disorder ◽

Tnf Α

AbstractAcute lung injury (ALI) represents a frequent sepsis-induced inflammatory disorder. Mesenchymal stromal cells (MSCs) elicit anti-inflammatory effects in sepsis. This study investigated the mechanism of exosomes from adipose-derived MSCs (ADMSCs) in sepsis-induced ALI. The IL-27r−/− (WSX-1 knockout) or wild-type mouse model of sepsis was established by cecal ligation and puncture (CLP). The model mice and lipopolysaccharide (LPS)-induced macrophages were treated with ADMSC-exosomes. The content of Dil-labeled exosomes in pulmonary macrophages, macrophages CD68+ F4/80+ in whole lung tissues, and IL-27 content in macrophages were detected. The mRNA expression and protein level of IL27 subunits P28 and EBI3 in lung tissue and the levels of IL-6, TNF-α, and IL-1β were measured. The pulmonary edema, tissue injury, and pulmonary vascular leakage were measured. In vitro, macrophages internalized ADMSC-exosomes, and ADMSC-exosomes inhibited IL-27 secretion in LPS-induced macrophages. In vivo, IL-27 knockout attenuated CLP-induced ALI. ADMSC-exosomes suppressed macrophage aggregation in lung tissues and inhibited IL-27 secretion. ADMSC-exosomes decreased the contents of IL-6, TNF-α, and IL-1β, reduced pulmonary edema and pulmonary vascular leakage, and improved the survival rate of mice. Injection of recombinant IL-27 reversed the protective effect of ADMSC-exosomes on sepsis mice. Collectively, ADMSC-exosomes inhibited IL-27 secretion in macrophages and alleviated sepsis-induced ALI in mice.

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Melatonin Attenuates Sepsis-Induced Acute Lung Injury Through Improvement of Epithelial Sodium Channel-Mediated Alveolar Fluid Clearance Via Activation of SIRT1/SGK1/Nedd4-2 Signaling Pathway

Frontiers in Pharmacology ◽

10.3389/fphar.2020.590652 ◽

2020 ◽

Vol 11 ◽

Author(s):

Jing Li ◽

Longfei Liu ◽

Xiaojun Zhou ◽

Xianzhou Lu ◽

Xianrong Liu ◽

...

Keyword(s):

Acute Lung Injury ◽

Lung Injury ◽

Sodium Channel ◽

Signaling Pathway ◽

Cecal Ligation ◽

Weight Ratio ◽

Epithelial Sodium Channel ◽

Enzyme Linked Immunosorbent Assay ◽

Alveolar Fluid Clearance ◽

Protein Expressions

Acute lung injury is characterized by alveolar vascular barrier injury, and protein-rich pulmonary oedema. Alveolar fluid clearance is closely related to the prognosis of patients with acute lung injury. Melatonin has been shown to have a protective effect on multiple organ injury induced by sepsis. In this study we investigated the effect of melatonin on alveolar fluid clearance (AFC) and explored its potential mechanisms in sepsis-induced acute lung injury. The cecal ligation and puncture was adopted to establish mouse sepsis model. Morphological changes of lung tissues with the hematoxylin staining were observed. AFC and lung wet/dry weight ratio were measured to assess pulmonary edema. Inflammatory mediators in bronchoalveolar lavage fluid were analyzed via enzyme-linked immunosorbent assay. NAD+/NADH and SIRT1 activity were measured by colorimetric assay kit. The protein expressions of epithelial sodium channel (ENaC), silent information regulator1 (SIRT1), SGK1 and Nedd4-2 were immunoblotted by western blot in vivo and in vitro. The distribution of α-ENaC and SIRT1 was detected by immunofluorescence. We found that melatonin attenuated sepsis induced lung injury, improved survival rate, enhanced alveolar fluid clearance, improved SIRT1 activity, increased protein expressions of SIRT1 and ENaC, and activated SGK1/Nedd4-2 pathway. Furthermore, SIRT1 inhibitor EX527 counteracted the effects of melatonin on alveolar fluid clearance and ENaC. These results revealed that melatonin enhanced ENaC-mediated AFC via the SIRT1/SGK1/Nedd4-2 signaling pathway. Our study demonstrated that melatonin might provide a novel therapeutic strategy for sepsis-induced acute lung injury.

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MEF2C alleviates acute lung injury in cecal ligation and puncture (CLP)-induced sepsis rats by up-regulating AQP1

Allergologia et Immunopathologia ◽

10.15586/aei.v49i5.477 ◽

2021 ◽

Vol 49 (5) ◽

pp. 117-124

Author(s):

Wenmei Liang ◽

Li Guo ◽

Tonghua Liu ◽

Song Qin

Keyword(s):

Acute Lung Injury ◽

Lung Injury ◽

Inflammatory Response ◽

Cecal Ligation ◽

Weight Ratio ◽

Dry Weight ◽

Tunel Staining ◽

Cecal Ligation And Puncture ◽

Tnf Α ◽

Factor Α

Background: Sepsis is a systemic inflammatory response syndrome and leads to patient’s death. Objective: To investigate the effect of myocyte enhancer factor 2 (MEF2C) on acute lung injury (ALI) with sepsis and its possible mechanism.Material and Methods: The cecal ligation and puncture (CLP)-induced sepsis rat model was established. The lung injury was determined by lung wet–dry weight ratio, the concentration of inflammatory cytokines, including tumor necrosis factor-α (TNF-α), Interlukin (IL)-6, IL-1β, and IL-10, were measured by the enzyme-linked-immunosorbent serologic assay kit. The cell apoptosis was detected by TUNEL staining assay.Results: Interestingly, MEF2C was down-regulated in this model. Moreover, adeno-associated virus (AAV)-MEF2C treatment markedly suppressed TNF-α, IL-1β, and IL-6 concentrations but promoted IL-10 concentration in serum in CLP-challenged rats. Besides, overexpression of MEF2C alleviates CLP-induced lung injury. Interestingly, AAV-MEF2C treatment was confirmed to suppress apoptosis in CLP-induced sepsis rats as well as promote aquaporin APQ1 expres-sion. Mechanistically, the rescue experiments indicated that MEF2C alleviated CLP-induced lung inflammatory response and apoptosis via up-regulating AQP1.Conclusion: In summary, overexpression of MEF2C suppressed CLP-induced lung inflamma-tory response and apoptosis via up-regulating AQP1, providing a novel therapeutic target for sepsis-induced ALI.

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Dexmedetomidine Promotes Alveolar Fluid Clearance by Upregulating Na,K-ATPase Expression in a Rat Model of Acute Lung Injury via α2 AR/PI3K/Akt Pathway

10.21203/rs.3.rs-532699/v1 ◽

2021 ◽

Author(s):

Mingzhu Xia ◽

Zhi Huang ◽

Mingyu Xu ◽

Chao Hai ◽

Wenbo Diao ◽

...

Keyword(s):

Acute Lung Injury ◽

Lung Injury ◽

Pulmonary Edema ◽

Molecular Mechanisms ◽

A549 Cells ◽

Lung Injury Score ◽

Alveolar Fluid Clearance ◽

Apoptosis Rate ◽

Tnf Α

Abstract Our previous studies have shown that Dexmedetomidine (Dex), α2 adrenergic receptor (α2AR) agonist, reduces pulmonary edema in LPS-induced acute lung injury (ALI), but the mechanism is not clear. The purpose of this study is to explore whether Dex promotes AFC by upregulating the expression of Na,K-ATPase in LPS-induced ALI and possible molecular mechanisms. Histology of the lungs was assayed with H-E staining, and the lung injury score was calculated. PaO2, PaO2/FiO2 , the lung index, wet/dry (W/D) ratio of the lung tissues and alveolar fluid clearance(AFC) was measured; The concentrations of TNF-α, IL-1β, IL-6 in bronchoalveolar lavage fluid (BALF) and serum were measured. Myeloperoxidase (MPO) activity in lung tissues were determined. The apoptosis rate of A549 cells and the expression of Bcl-2 and Bax were evaluated. The expression of Na,K-ATPase , p-PI3K and p-Akt in vivo and in vitro were evaluated. Dex significantly alleviated lung tissue injury induced by LPS. Dex treatment reduced the W/D, lung index and MPO activity, increased PaO2, PaO2/FiO2 and AFC in LPS-induced ALI. In addition, Dex reduced the concentrations of TNF-α, IL-β and IL-6 in BALF and serum. Dex reduced the apoptosis rate, up-regulated the expression of Bcl-2 and down-regulated the expression of Bax in LPS-stimulated A549 cells. Furthermore, Dex increased the expression of α1Na,K-ATPase, β1 Na,K-ATPase and p-PI3K , p-Akt in vivo and vitro. However, these effects of Dex were partially reversed by the α2AR inhibitor yohim-bine or PI3K inhibitor LY294002. Collectively, these results suggest that Dex attenuates pulmonary edema by stimulating AFC via upregulating the Na,K-ATPase expressi-on in LPS-induced acute lung injury by modulating the α2AR/PI3K/Akt signaling pathway.

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The Role of Vagus Nerve on Dexmedetomidine Induced Survival and Lung Protection in a Sepsis Model in Rats.

10.21203/rs.3.rs-483367/v1 ◽

2021 ◽

Author(s):

Yumo Li ◽

Binbin Wu ◽

Cong Hu ◽

Jie Hu ◽

Qingquan Lian ◽

...

Keyword(s):

Acute Lung Injury ◽

Lung Injury ◽

Vagus Nerve ◽

Vagal Nerve ◽

Lung Injury Score ◽

Enzyme Linked Immunosorbent Assay ◽

Protective Effects ◽

Lung Protection ◽

Tnf Α

Abstract BackgroundSepsis often results in acute lung injury (ALI). Sedative dexmedetomidine (Dex) was reported to protect cells and organs due to its direct cellular effects. This study aims to investigate the role of vagus nerves on Dex induced lung protection in a model of lipopolysaccharide (LPS)-induced ALI in rats. MethodsThe bilateral cervical vagus nerve of male Sprague-Dawley rats was sectioned or just exposed without section as sham surgery. The ALI was induced by intraperitoneal injection of LPS (1 or 10 mg/kg). After LPS administration, Dex antagonist yohimbine (YOH) (1 mg/kg) and/or Dex (25 μg/kg) was injected intraperitoneally at 0, 4, 8 and 12 hours to rats with or without vagotomy. The severity of ALI was determined with survival curve analysis and lung pathological scores of haematoxylin and eosin (H-E) staining sections. The plasma concentrations of interleukin 1beta (IL-1β), tumour necrosis factor-alpha (TNF-α), catecholamine (CA) and acetylcholine (Ach) were measured with enzyme-linked immunosorbent assay (ELISA). ResultsThe median survival time of LPS-induced ALI rats was significantly prolonged by Dex (22 hours, 50% CI, [31.25, 90.63]) compared that in the LPS group (14 hours, 50% CI, [18.75, 81.25], P < 0.05), and the acute lung injury score was significantly reduced by Dex (6.5, 50% CI, [5.75, 7.5] vs 11.5, 50% CI, [10.75, 12.50] in the LPS group, P < 0.01). However, these protective effects of Dex were significantly reduced by either YOH administration or vagotomy. Dex significantly decreased LPS-induced plasma IL-1β (pg/ml) (20.75 ± 0.78 vs. 30.22 ± 2.62, P < 0.01), TNF-α (pg/ml) (205.30 ± 9.39 vs. 273.40 ± 14.50, P < 0.01), and CA (pg/ml) (825.70 ± 43.46 vs. 1188.00 ± 64.40, P < 0.01) but increased the secretion of Ach (pg/ml) (507.20 ± 49.52 vs. 296.50 ± 62.44, P < 0.01); these effects of Dex was partially abolished by vagotomy. ConclusionsOur data suggested that Dex increased vagal nerve tone which partially contributed to its anti-inflammatory and lung protective effects. The indirect anti-inflammation and direct cytoprotection of Dex are likely through high vagal nerve tone and α 2 -adrenoceptor activation, respectively.

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Pristimerin attenuates sepsis-induced lung injury by regulating nuclear factor kappaB/high-mobility group box 1 pathway

Tropical Journal of Pharmaceutical Research ◽

10.4314/tjpr.v19i6.7 ◽

2020 ◽

Vol 19 (6) ◽

pp. 1167-1171

Author(s):

Xiao Wang ◽

Lei Huang ◽

Peng Li

Keyword(s):

Lung Injury ◽

Lung Tissue ◽

Inflammatory Mediators ◽

Cecal Ligation ◽

Weight Ratio ◽

High Mobility ◽

Dry Weight ◽

Serum Levels ◽

High Mobility Group ◽

Lung Injury Score

Purpose: To determine the effect of pristimerin on sepsis-induced lung injury, and the underlying mechanism of action.Methods: Lung injury was established in mice via induction of sepsis through cecal ligation and puncture (CLP). The effect of pristimerin was evaluated based on lung wet/dry weight and PaO2/FiO2 ratios. Lung tissue was subjected to immunohistochemical and histopathological analyses, as well as Western blotting. Furthermore, the serum levels of inflammatory mediators were determined.Results: Pristimerin reversed the altered lung wet/dry weight ratio and PaO2/FiO2 ratio in the lung, and also reduced lung injury score, relative to CLP group (p < 0.05). Moreover, it suppressed nucleocytoplasmic translocation of high mobility group protein B1 (HMGB1) in lung tissue. Serum levels of inflammatory mediators and expression levels of inducible nitric oxide synthase and nuclear factorkappaB p65 were significantly reduced by pristimerin (p < 0.05).Conclusion: Pristimerin ameliorates sepsis-induced lung injury by inhibiting HMGB1/NF-κB. Thus, this compound has a potential for clinical application in the management of lung injury. Keywords: Pristimerin, Sepsis, Lung injury, Inflammatory mediators, HMGB1

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

Experimental & Molecular Medicine ◽

10.1038/s12276-021-00651-6 ◽

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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Tumor necrosis factor-α small interfering RNA alveolar epithelial cell-targeting nanoparticles reduce lung injury in C57BL/6J mice with sepsis

Journal of International Medical Research ◽

10.1177/0300060520984652 ◽

2021 ◽

Vol 49 (1) ◽

pp. 030006052098465

Author(s):

Like Qian ◽

Xi Yin ◽

Jiahao Ji ◽

Zhengli Chen ◽

He Fang ◽

...

Keyword(s):

Tumor Necrosis Factor ◽

Epithelial Cell ◽

Lung Injury ◽

Tumor Necrosis ◽

Alveolar Epithelial Cell ◽

Weight Ratio ◽

B Cell Lymphoma ◽

Alveolar Epithelial ◽

Tnf Α ◽

Necrosis Factor

Background The role of tumor necrosis factor (TNF)-α small interfering (si)RNA alveolar epithelial cell (AEC)-targeting nanoparticles in lung injury is unclear. Methods Sixty C57BL/6J mice with sepsis were divided into normal, control, sham, 25 mg/kg, 50 mg/kg, and 100 mg/kg siRNA AEC-targeting nanoparticles groups (n = 10 per group). The wet:dry lung weight ratio, and hematoxylin and eosin staining, western blotting, and enzyme-linked immunosorbent assays for inflammatory factors were conducted to compare differences among groups. Results The wet:dry ratio was significantly lower in control and sham groups than other groups. TNF-α siRNA AEC-targeting nanoparticles significantly reduced the number of eosinophils, with significantly lower numbers in the 50 mg/kg group than in 25 mg/kg and 100 mg/kg groups. The nanoparticles also significantly reduced the expression of TNF-α, B-cell lymphoma-2, caspase 3, interleukin (IL)-1β, and IL-6, with TNF-α expression being significantly lower in the 50 mg/kg group than in 25 mg/kg and 100 mg/kg groups. Conclusion TNF-α siRNA AEC-targeting nanoparticles appear to be effective at improving lung injury-related sepsis, and 50 mg/kg may be a preferred dose option for administration.

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LncRNA HOTAIR Increases Inflammatory Responses by Activating NF-κB Pathway in LPS-Induced Acute Lung Injury

10.21203/rs.3.rs-49969/v1 ◽

2020 ◽

Author(s):

XiaoMei Huang ◽

ZeXun Mo ◽

YuJun Li ◽

Hua He ◽

KangWei Wang ◽

...

Keyword(s):

Acute Lung Injury ◽

Lung Injury ◽

Noncoding Rna ◽

Nuclear Translocation ◽

Inflammatory Responses ◽

A549 Cells ◽

Enzyme Linked Immunosorbent Assay ◽

Qrt Pcr ◽

Tnf Α ◽

Lncrna Hotair

Abstract Background Nuclear factor kappa-B (NF-κB) activation increased the expression of cytokines and further lead to lung injury was considered the main mechanism of acute lung injury (ALI). Here, we focus on exploring the potential regulatory mechanism between long noncoding RNA (LncRNA) HOX transcript antisense RNA (HOTAIR) and NF-κB on LPS-induced ALI. Methods A549 cells were then divided into 4 groups: HOTAIR group, NC group, si-HOTAIR group and si-NC group. These 4 groups were then treated with 1μg/mL lipopolysaccharides (LPS) or without LPS at 37°C for 24 h. The expression level of cytokines (tumor necrosis factor (TNF)-α, interleukin (IL)-1β and IL-6) and LncRNA HOTAIR were evaluated by quantitative Real Time Polymerase Chain Reaction (qRT-PCR) and Enzyme-linked immunosorbent assay (ELISA). Western Blot analysis was adopted for evaluating the level of p-IκBα/IκBα and p-p65/p65. Nuclear translocation of p65 was observed by immunofluorescence staining. Results qRT-PCR and ELISA assay showed that the expression of cytokines (IL-1β, IL-6 and TNF-α) and inflammatory gene HOTAIR was remarkably increased with LPS treatment (p < 0.01). Over-expression of HOTAIR significantly increased the expression of cytokines (including IL-1β, IL-6 and TNF-α) and NF-κB pathway associated proteins (including p-IκBα/IκBα and p-p65/p65), while knockdown of HOTAIR had the opposite effect (p < 0.01). The immunofluorescence assay showed that the level of p65 in the nucleus was significantly higher in the HOTAIR group and significantly lowers in the si-HOTAIR group (p < 0.01). Conclusion HOTAIR may play a pro-inflammatory response through NF-κB pathway in LPS-induced ALI, which may provide a perspective for further understanding the pathogenic mechanism of ALI.

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