Viola yedoensis Liposoluble Fraction Ameliorates Lipopolysaccharide-Induced Acute Lung Injury in Mice

2012 ◽  
Vol 40 (05) ◽  
pp. 1007-1018 ◽  
Author(s):  
Wen Li ◽  
Jun-Yun Xie ◽  
Hong Li ◽  
Yun-Yi Zhang ◽  
Jie Cao ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Chemical Constituents ◽  
Chinese Herb ◽  
Weight Ratio ◽  
Acute Injury ◽  
Myeloperoxidase Activity ◽  
Proinflammatory Mediators

Viola yedoensis is a component of traditional Chinese herb medicine for inflammatory diseases. Chemical constituents of V. yedoensis have been shown to possess antibacterial, anti-HIV, and anticoagulant effects in experimental research; however, their anti-inflammatory properties remain to be demonstrated. In this study, a mouse model of lipopolysaccharide (LPS)-induced acute lung injury was used to investigate the effect of petroleum ether fraction of V. yedoensis (PEVY) on inflammation in vivo. After being shown to have anti-complementary activity in vitro, PEVY was orally administered to the mice at doses of 2, 4, and 8 mg/kg. Treatment with PEVY significantly decreased the wet-to-dry weight ratio of the lung, total cells, red blood cells, protein concentration, and myeloperoxidase activity in bronchoalveolar lavage fluid. PEVY markedly attenuated lung injury with improved lung morphology and reduced complement deposition. In addition, PEVY suppressed the expression of pro-inflammatory cytokines, TNF-α, IL-1β, and IL-6. Taken together, PEVY protects the lung from acute injury, potentially via inhibiting the activation of the complement system and excessive production of proinflammatory mediators.

Interactions between CBP, NF-κB, and CREB in the lungs after hemorrhage and endotoxemia

2001 ◽  
Vol 281 (2) ◽  
pp. L418-L426 ◽  
Author(s):  
Robert Shenkar ◽  
Ho-Kee Yum ◽  
John Arcaroli ◽  
John Kupfner ◽  
Edward Abraham
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Xanthine Oxidase ◽  
Binding Protein ◽  
Camp Response Element Binding ◽  
Creb Binding Protein ◽  
Proinflammatory Mediators ◽  
Element Binding Protein

The transcriptional regulatory factor nuclear factor (NF)-κB has a central role in modulating expression of proinflammatory mediators that are important in acute lung injury. In vitro studies have shown that competition between NF-κB and cAMP response element binding protein (CREB) for binding to the coactivator CREB-binding protein (CBP) is important in regulating transcriptional activity of these factors. In the present study, we examined in vivo interactions between CBP, CREB, and NF-κB in hemorrhage- or endotoxemia-induced acute lung injury. Association of CBP with CREB or the p65 subunit of NF-κB increased in the lungs after hemorrhage or endotoxemia. Inhibition of xanthine oxidase before hemorrhage, but not before endotoxemia, decreased p65-CBP interactions while increasing those between CREB and CBP. These alterations in CREB-CBP and p65-CBP interactions were functionally significant because xanthine oxidase inhibition before hemorrhage resulted in increased expression of the CREB-dependent gene c-Fos and decreased expression of macrophage inflammatory protein-2, a NF-κB-dependent gene. The present results show that the coactivator CBP has an important role in modulating transcription in vivo under clinically relevant pathophysiological conditions.

scholarly journals Three Ingredients of Safflower Alleviate Acute Lung Injury and Inhibit NET Release Induced by Lipopolysaccharide

2020 ◽  
Vol 2020 ◽  
pp. 1-12 ◽  
Author(s):  
Yun-peng Wang ◽  
Yu Guo ◽  
Ping-shan Wen ◽  
Zhen-zhen Zhao ◽  
Jian Xie ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Chinese Herb ◽  
Weight Ratio ◽  
Mitogen Activated Protein Kinase ◽  
Inflammatory Factors ◽  
Vitro Assay ◽  
Net Release ◽  
Three Components

Xuebijing injection is a Chinese herb compound to treat sepsis in China, but it contains many different kinds of components, and each component may have different effects in treating sepsis. The present study was performed to investigate the effect of three ingredients of Xuebijing, safflor yellow A (SYA), hydroxysafflor yellow A (HSYA), and anhydrosafflor yellow B (AHSYB), in lipopolysaccharide- (LPS-) induced acute lung injury (ALI). LPS (10 mg/kg) was injected intratracheally to induce acute lung injury in mice, which were then treated with SYA, HSYA, and AHSYB. The blood, bronchoalveolar lavage fluid (BALF), and lung tissues were collected to detect degree of lung injury, level of inflammation, and neutrophil extracellular traps (NETs). In vitro experiments were performed using HL-60 cells stimulated with phorbol myristate acetate (PMA). Lung injury induced by LPS was alleviated by SYA, HSYA, and AHSYB as demonstrated by the histopathologic test. The three components inhibit LPS-induced elevation of the levels of inflammatory factors and wet-to-dry weight ratio as well as the amount of protein and cells in the BALF. They also induced a remarkably less overlay of myeloperoxidase (MPO) and histone in the immunofluorescence assay and reduced level of MPO-DNA complex in plasma. The in vitro assay showed a similar trend that the three components inhibited PMA-induced NET release in neutrophil-like HL-60 cells. Western blot demonstrated that phosphorylation of c-rapidly accelerated fibrosarcoma (c-Raf), mitogen-activated protein kinase ERK kinase (MEK), and extracellular signal-regulated kinase (ERK) in the lungs of LPS-challenged mice, and PMA-treated HL-60 cells were all significantly reduced by SYA, HSYA, and AHSYB. Therefore, our data demonstrated that three components of XBJ, including SYA, HSYA, and AHSYB, showed a protective effect against LPS-induced lung injury and NET release.

scholarly journals The mechanism of nicotinamide on reducing acute lung injury by inhibiting MAPK and NF-κB signal pathway

2021 ◽  
Vol 27 (1) ◽  
Author(s):  
Qun Zhang ◽  
Junyao Li ◽  
Haixia Zhong ◽  
Yanling Xu
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Signaling Pathways ◽  
Cell Damage ◽  
Signal Pathway ◽  
Mechanistic Studies ◽  
Qrt Pcr ◽  
Proinflammatory Mediators

Abstract Background Acute lung injury is an important factor that leads to the death of patients with pneumonia. Previous studies have shown that nicotinamide (NAM) plays a role in reducing cell damage, so this study explored the mechanism by which NAM functions in acute lung injury. Methods We explored the mechanism by which NAM affects acute lung injury in vivo and in vitro by qRT-PCR, western blotting and ELISA. Results The results showed that NAM could significantly reduce lung injury and proinflammatory mediator accumulation. Further mechanistic studies showed that NAM could significantly inhibit the MAPK and AKT/NF-κB signaling pathways. Conclusion These results suggested that NAM may reduce the release of proinflammatory mediators by inhibiting the MAPK and AKT/NF-κB signaling pathways and ultimately alleviate 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 Group V Phospholipase A2 Mediates Endothelial Dysfunction and Acute Lung Injury Caused by Methicillin-Resistant Staphylococcus aureus

Cells ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1731
Author(s):  
Yu Maw Htwe ◽  
Huashan Wang ◽  
Patrick Belvitch ◽  
Lucille Meliton ◽  
Mounica Bandela ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Acute Lung Injury ◽  
Endothelial Dysfunction ◽  
Lung Injury ◽  
Phospholipase A2 ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Group V ◽  
Methicillin Resistant

Lung endothelial dysfunction is a key feature of acute lung injury (ALI) and clinical acute respiratory distress syndrome (ARDS). Previous studies have identified the lipid-generating enzyme, group V phospholipase A2 (gVPLA2), as a mediator of lung endothelial barrier disruption and inflammation. The current study aimed to determine the role of gVPLA2 in mediating lung endothelial responses to methicillin-resistant Staphylococcus aureus (MRSA, USA300 strain), a major cause of ALI/ARDS. In vitro studies assessed the effects of gVPLA2 inhibition on lung endothelial cell (EC) permeability after exposure to heat-killed (HK) MRSA. In vivo studies assessed the effects of intratracheal live or HK-MRSA on multiple indices of ALI in wild-type (WT) and gVPLA2-deficient (KO) mice. In vitro, HK-MRSA increased gVPLA2 expression and permeability in human lung EC. Inhibition of gVPLA2 with either the PLA2 inhibitor, LY311727, or with a specific monoclonal antibody, attenuated the barrier disruption caused by HK-MRSA. LY311727 also reduced HK-MRSA-induced permeability in mouse lung EC isolated from WT but not gVPLA2-KO mice. In vivo, live MRSA caused significantly less ALI in gVPLA2 KO mice compared to WT, findings confirmed by intravital microscopy assessment in HK-MRSA-treated mice. After targeted delivery of gVPLA2 plasmid to lung endothelium using ACE antibody-conjugated liposomes, MRSA-induced ALI was significantly increased in gVPLA2-KO mice, indicating that lung endothelial expression of gVPLA2 is critical in vivo. In summary, these results demonstrate an important role for gVPLA2 in mediating MRSA-induced lung EC permeability and ALI. Thus, gVPLA2 may represent a novel therapeutic target in ALI/ARDS caused by bacterial infection.

scholarly journals H2S in acute lung injury: a therapeutic dead end(?)

2020 ◽  
Vol 8 (S1) ◽  
Author(s):  
Tamara Merz ◽  
Nicole Denoix ◽  
Martin Wepler ◽  
Holger Gäßler ◽  
David A. C. Messerer ◽  
...  
Keyword(s):  
Hydrogen Sulfide ◽  
Acute Lung Injury ◽  
Lung Injury ◽  
Circulatory Shock ◽  
Therapeutic Window ◽  
Pharmacokinetics And Pharmacodynamics ◽  
Clinical Reality ◽  
Dead End

AbstractThis review addresses the plausibility of hydrogen sulfide (H2S) therapy for acute lung injury (ALI) and circulatory shock, by contrasting the promising preclinical results to the present clinical reality. The review discusses how the narrow therapeutic window and width, and potentially toxic effects, the route, dosing, and timing of administration all have to be balanced out very carefully. The development of standardized methods to determine in vitro and in vivo H2S concentrations, and the pharmacokinetics and pharmacodynamics of H2S-releasing compounds is a necessity to facilitate the safety of H2S-based therapies. We suggest the potential of exploiting already clinically approved compounds, which are known or unknown H2S donors, as a surrogate strategy.

scholarly journals Down-regulation of SNHG16 alleviates the acute lung injury in sepsis rats through miR-128-3p/HMGB3 axis

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Junli Sun ◽  
Keke Xin ◽  
Chenghui Leng ◽  
Jianlin Ge
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Western Blot ◽  
Cell Viability ◽  
Inflammatory Diseases ◽  
Cecal Ligation ◽  
Inflammatory Factors ◽  
Lung Epithelial

Abstract Background Long noncoding RNAs contribute to various inflammatory diseases, including sepsis. We explore the role of small nucleolar RNA host gene 16 (SNHG16) in sepsis-mediated acute lung injury (ALI) and inflammation. Methods A sepsis-induced ALI rat model was constructed by the cecal ligation and perforation method. The profiles of SNHG16, miR-128-3p, and high-mobility group box 3 (HMGB3) were monitored by quantitative reverse transcription PCR and Western blot. The pathologic changes of lung tissues were evaluated by Hematoxylin–Eosin staining, immunohistochemistry, and dry and wet method. Meanwhile, the pro-inflammatory factors and proteins were determined by ELISA and Western blot. In contrast, a sepsis model in BEAS-2B was induced with lipopolysaccharide (LPS) to verify the effects of SNHG16/miR-128-3p/HMGB3 on lung epithelial cell viability and apoptosis. Results As a result, SNHG16 and HMGB3 were up-regulated, while miR-128-3p was down-regulated in sepsis-induced ALI both in vivo and in vitro. Inhibiting SNHG16 reduced the apoptosis and inflammation in the sepsis-induced ALI model. Overexpressing SNHG16 promoted LPS-mediated lung epithelial apoptosis and inhibited cell viability and inflammation, while miR-128-3p had the opposite effects. Mechanistically, SNHG16 targeted miR-128-3p and attenuated its expression, while miR-128-3p targeted the 3′ untranslated region of HMGB3. Conclusions Overall, down-regulating SNHG16 alleviated the sepsis-mediated ALI by regulating miR-128-3p/HMGB3.

Abstract 73: Bone Morphogenetic Protein Activity Modulates Endothelial Barrier Function

2012 ◽  
Vol 32 (suppl_1) ◽  
Author(s):  
Thomas Helbing ◽  
Elena Ketterer ◽  
Bianca Engert ◽  
Jennifer Heinke ◽  
Sebastian Grundmann ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Barrier Function ◽  
Endothelial Permeability ◽  
Bmp Signaling ◽  
Endothelial Barrier ◽  
Endothelial Barrier Function

Introduction: Acute lung injury (ALI) and its more severe form, acute respiratory distress syndrome, are associated with high morbidity and mortality in patients. During the progression of ALI, the endothelial cell barrier of the pulmonary vasculature becomes compromised, leading to pulmonary edema, a characteristic feature of ALI. It is well-established that EC barrier dysfunction is initiated by cytoskeletal remodeling, which leads to disruption of cell-cell contacts and formation of paracellular gaps, allowing penetration of protein-rich fluid and inflammatory cells. Bone morphogenetic proteins (BMPs) are important players in endothelial dysfunction and inflammation but their effects on endothelial permeability in ALI have not been investigated until now. Methods and Results: As a first approach to assess the role of BMPs in acute lung injury we analysed BMP4 and BMPER expression in an infectious (LPS) and a non-infectious (bleomycin) mouse models of acute lung injury. In both models BMP4 and BMPER protein expression levels were reduced demonstrated by western blots, suggesting that BMPs are involved in progression ALI. To assess the role of BMPs on vascular leakage, a key feature of ALI, BMP activity in mice was inhibited by i.p. administration of LDN193189, a small molecule that blocks BMP signalling. After 3 days Evans blue dye (EVB) was administered i.v. and dye extravasation into the lungs was quantified as a marker for vascular leakage. Interestingly, LDN193189 significantly increased endothelial permeability compared to control lungs, indicating that BMP signaling is involved in maintenance of endothelial barrier function. To quantify effects of BMP inhibition on endothelial barrier function in vitro, HUVECs were seeded onto transwell filters and were exposed to LDN193189. After 3 days FITC-dextrane was added and passage into the lower chamber was quantified as a marker for endothelial barrier function. Thrombin served as a positive control. As expected from our in vivo experiments inhibition of BMP signaling by LDN193189 enhanced FITC-dextrane passage. To study specific effects of BMPs on endothelial barrier function, two protagonist of the BMP family, BMP2 and BMP4, or BMP modulator BMPER were tested in the transwell assay in vitro. Interestingly BMP4 and BMPER, but not BMP2, reduced FITC-dextrane passage demonstrating that BMP4 and BMPER improved endothelial barrier function. Vice versa, specific knock down of BMP4 or BMPER increased leakage in transwell assays. Im immuncytochemistry silencing of BMPER or BMP4 induced hyperpermeability as a consequence of a pro-inflammatory endothelial phenotype characterised by reduced cell-cell contacts and increased actin stress fiber formation. Additionally, the pro-inflammatory endothelial phenotype was confirmed by real-time revealing increased expression of adhesion molecules ICAM-1 or proinflammatory cytokines such as IL-6 and IL-8 in endothelial cells after BMPER or BMP4 knock down. Confirming these in vitro results BMPER +/- mice exhibit increased extravasation of EVB into the lungs, indicating that partial loss of BMPER impairs endothelial barrier function in vitro and in vivo. Conclusion: We identify BMPER and BMP4 as local regulators of vascular permeability. Both are protective for endothelial barrier function and may open new therapeutic avenues in the treatment of acute lung injury.

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