scholarly journals Protective Effects of Berry Volatiles on Lipopolysaccharide-Induced Acute Lung Injury in Human A549 Cells

2021 ◽  
Vol 5 (Supplement_2) ◽  
pp. 315-315
Author(s):  
Inah Gu ◽  
Cindi Brownmiller ◽  
Luke Howard ◽  
Sun-Ok Lee
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Cell Viability ◽  
Inflammatory Cytokines ◽  
Lung Inflammation ◽  
A549 Cells ◽  
Black Raspberry ◽  
Elisa Kit ◽  
Pro Inflammatory Cytokines ◽  
Inflammatory Effect

Abstract Objectives Berry volatiles are primary or secondary compounds produced when tissue disrupts, and responsible for the flavor and aroma of berries. Berry volatiles has been recently reported to have anti-inflammatory effect. Acute lung injury is one of the severe consequences of lung inflammation increasing respiratory stress and pulmonary edema with high mortality. Thus, the objective of this study was to investigate the anti-inflammatory effect of three berry volatiles (blackberry, black raspberry, and blueberry) on lipopolysaccharide (LPS)-induced acute lung injury in lung epithelial A549 cells and its mechanism. Methods A549 cells were pretreated with three different dilutions (2, 4, and 8-fold) of blackberry, black raspberry, and blueberry volatile extract for 1 h. Cells were then stimulated with or without LPS (10 μg/mL) for 24 h. The cell viability was measured with one-step diphenyl tetrazolium bromide (MTS) assay. The level of pro-inflammatory cytokines in the culture media was examined by using enzyme-linked immunosorbent assay (ELISA) kit. Apoptosis of A549 cells were evaluated by using death detection ELISA kit. All statistical tests were analyzed by using one-way ANOVA, followed by Tukey's multiple comparisons. Significant difference was defined at P < 0.05. Results Two-fold diluted berry volatiles (blackberry, black raspberry, and blueberry) significantly decreased A549 cell viability by 24%, 52% and 61%, respectively compared to the control (P < 0.05). Concentration of interleukin-8 (IL-8) was remarkably higher when LPS stimulated A549 cells compared to the control (P < 0.05). However, 2-fold diluted berry volatiles significantly suppressed LPS-induced IL-8 level compared to LPS treated group (P < 0.01). 2-fold diluted blackberry, black raspberry, and blueberry volatiles also showed significant apoptotic effect on A549 cells compared to the control (P < 0.05). Conclusions These results showed that blackberry, black raspberry, and blueberry volatiles suppress inflammatory responses by modulating pro-inflammatory cytokines and apoptosis. This study suggests that volatiles from berries (blackberry, black raspberry, and blueberry) may have a potential impact on lung inflammation. Funding Sources Arkansas Biosciences Institute.

scholarly journals Essential Role of Visfatin in Lipopolysaccharide and Colon Ascendens Stent Peritonitis-Induced Acute Lung Injury

2019 ◽  
Vol 20 (7) ◽  
pp. 1678 ◽  
Author(s):  
Yi-Chen Lee ◽  
Chun-Yu Lin ◽  
Yen-Hsu Chen ◽  
Wen-Chin Chiu ◽  
Yen-Yun Wang ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Epithelial Cell ◽  
Lung Injury ◽  
Cell Lines ◽  
Inflammatory Cytokines ◽  
Bronchial Epithelial Cell ◽  
Bronchial Epithelial ◽  
Epithelial Cell Lines ◽  
Nfκb Pathway ◽  
Pro Inflammatory Cytokines

Acute lung injury (ALI) is a life-threatening syndrome characterized by acute and severe hypoxemic respiratory failure. Visfatin, which is known as an obesity-related cytokine with pro-inflammatory activities, plays a role in regulation of inflammatory cytokines. The mechanisms of ALI remain unclear in critically ill patients. Survival in ALI patients appear to be influenced by the stress generated by mechanical ventilation and by ALI-associated factors that initiate the inflammatory response. The objective for this study was to understand the mechanisms of how visfatin regulates inflammatory cytokines and promotes ALI. The expression of visfatin was evaluated in ALI patients and mouse sepsis models. Moreover, the underlying mechanisms were investigated using human bronchial epithelial cell lines, BEAS-2B and NL-20. An increase of serum visfatin was discovered in ALI patients compared to normal controls. Results from hematoxylin and eosin (H&E) and immunohistochemistry staining also showed that visfatin protein was upregulated in mouse sepsis models. Moreover, lipopolysaccharide (LPS) induced visfatin expression, activated the STAT3/NFκB pathway, and increased the expression of pro-inflammatory cytokines, including IL1-β, IL-6, and TNF-α in human bronchial epithelial cell lines NL-20 and BEAS-2B. Co-treatment of visfatin inhibitor FK866 reversed the activation of the STAT3/NFκB pathway and the increase of pro-inflammatory cytokines induced by LPS. Our study provides new evidence for the involvement of visfatin and down-stream events in acute lung injury. Further studies are required to confirm whether the anti-visfatin approaches can improve ALI patient survival by alleviating the pro-inflammatory process.

Vanillin protects lipopolysaccharide-induced acute lung injury by inhibiting ERK1/2, p38 and NF-κB pathway

2019 ◽  
Vol 11 (16) ◽  
pp. 2081-2094 ◽  
Author(s):  
Tingting Guo ◽  
Zhenzhong Su ◽  
Qi Wang ◽  
Wei Hou ◽  
Junyao Li ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Western Blot ◽  
Lung Inflammation ◽  
Macrophage Activation ◽  
Myeloperoxidase Activity ◽  
Histopathological Changes ◽  
Tnf Α ◽  
Anti Inflammatory ◽  
Inflammatory Effect

Aim: Thus far, the anti-inflammatory effect of vanillin in acute lung injury (ALI) has not been studied. This study aimed to investigate the effect of vanillin in lipopolysaccharide (LPS)-induced ALI. Results & methodology: Our study detected the anti-inflammatory effects of vanillin by ELISA and western blot, respectively. Pretreatment of mice with vanillin significantly attenuated LPS-stimulated lung histopathological changes, myeloperoxidase activity and expression levels of proinflammatory cytokines by inhibiting the phosphorylation activities of ERK1/2, p38, AKT and NF-κB p65. In addition, vanillin inhibited LPS-induced TNF-α and IL-6 expression in RAW264.7 cells via ERK1/2, p38 and NF-κB signaling. Conclusion: Vanillin can inhibit macrophage activation and lung inflammation, which suggests new insights for clinical treatment of ALI.

The features of the course of virus-associated acute lung injury in mice with induced immunosuppression

2021 ◽  
Vol 21 (3) ◽  
pp. 75-80
Author(s):  
Andrey G. Aleksandrov
Keyword(s):  
Influenza Virus ◽  
Acute Lung Injury ◽  
Lung Injury ◽  
Inflammatory Cytokines ◽  
Influenza Infection ◽  
Lung Damage ◽  
Experimental Therapy ◽  
Blood Oxygen ◽  
Blood Oxygen Saturation ◽  
Pro Inflammatory Cytokines

BACKGROUND: Among all groups of patients with virus-associated acute lung injury with influenza infection, the most severe course is observed in patients with immunosuppression. In this case, despite the studied mechanism of the course of combined pathology, the question of therapy in this group of patients remains unclear. AIM: To study the features of the course of acute lung injury in influenza infection with secondary immunosuppression in an experiment for the possibility of searching for experimental therapy for this combined pathology. MATERIALS AND METHODS: The study was performed on 115 outbred female mice. The mouse-adapted pandemic influenza virus A/California/7/09MA (H1N1)pdm09 was used for modeling viral acute lung injury. Experimental immunosuppression was reproduced by administration of methotrexate (1.25 mg/kg intraperitoneally, once every 3 days during 3 weeks before infection). During the experiment, mortality, blood oxygen saturation, the concentration of pro-inflammatory cytokines in the lungs, and the severity of lung injury were measured. RESULTS: The presence of experimental immunosuppression led to an exacerbation of acute lung injury in infected animals in terms of mortality and lung damage. Changes in the dynamics of proinflammatory cytokines (TNF-, IL-6, IL-1) in the lungs were observed during acute lung injury. Retarded recovery of the lungs functional activity was noted. CONCLUSIONS: The experimental immunosuppression contributed to the exacerbation of acute lung injury and to an increase in the duration of the pathology. These changes could be associated with an altered process of elimination of the pathogen. The reproduced model of combined pathology was used for searching a therapy for these complications.

scholarly journals Ginsenoside Rg1 Regulates SIRT1 to Ameliorate Sepsis-Induced Lung Inflammation and Injury via Inhibiting Endoplasmic Reticulum Stress and Inflammation

2019 ◽  
Vol 2019 ◽  
pp. 1-10 ◽  
Author(s):  
Qian-Lu Wang ◽  
Lei Yang ◽  
Yue Peng ◽  
Min Gao ◽  
Ming-Shi Yang ◽  
...  
Keyword(s):  
Lung Injury ◽  
Er Stress ◽  
Inflammatory Cytokines ◽  
Lung Inflammation ◽  
A549 Cells ◽  
Mouse Lung ◽  
Ginsenoside Rg1 ◽  
Marker Proteins

Objectives. To investigate the protective effect of ginsenoside Rg1 on relieving sepsis-induced lung inflammation and injury in vivo and in vitro. Methods. Cultured human pulmonary epithelial cell line A549 was challenged with LPS to induce cell injury, and CLP mouse model was generated to mimic clinical condition of systemic sepsis. Rg1 was applied to cells or animals at indicated dosage. Apoptosis of cultured cells was quantified by flow cytometry, along with ELISA for inflammatory cytokines in supernatant. For septic mice, lung tissue pathology was examined, plus ELISA assay for serum cytokines. Western blotting was used to examine the activation of inflammatory pathways and ER stress marker proteins in both cells and mouse lung tissues. Reactive oxygen species (ROS) level was quantified by DCFDA kit. Results. Ginsenoside Rg1 treatment remarkably suppressed apoptosis rate of LPS-induced A549 cells, relieved mouse lung tissue damage, and elevated survival rate. Rg1 treatment also rescued cells from LPS-induced intracellular ROS. In both A549 cells and mouse lung tissues, further study showed that Rg1 perfusion significantly suppressed the secretion of inflammatory cytokines including tumor necrosis factor- (TNF-) alpha and interleukin- (IL-) 6 and relieved cells from ER stress as supported by decreased expression of marker proteins via upregulating sirtuin 1 (SIRT1). Conclusion. Our results showed that ginsenoside Rg1 treatment effectively relieved sepsis-induced lung injury in vitro and in vivo, mainly via upregulating SIRT1 to relieve ER stress and inflammation. These findings provide new insights for unrevealing potential candidate for severe sepsis accompanied with lung injury.

scholarly journals Identification of Atypical Mitogen-Activated Protein Kinase MAPK4 as A Novel Regulator in Acute Lung Injury

2020 ◽  
Author(s):  
Ling Mao ◽  
Ya Zhou ◽  
Longqing Chen ◽  
Lin Hu ◽  
Shiming Liu ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Survival Time ◽  
Inflammatory Cytokines ◽  
Mitogen Activated Protein Kinase ◽  
Lps Challenge ◽  
Mitogen Activated Protein ◽  
Pre Treatment ◽  
Pro Inflammatory Cytokines

Abstract Background: Acute lung injury (ALI) is a serious disease with highly morbidity and mortality that causes serious health problems worldwide. Atypical mitogen activated protein kinases (MAPKs) play critical roles in the development of tissues and have been proposed as promising therapeutic targets for various diseases. However, the potential role of atypical MAPKs in ALI remains elusive. In this study, we investigated the role of atypical MAPKs family member MAPK4 in ALI using LPS-induced murine ALI model. Results: We found that MAPK4 deficiency mice exhibited prolonged survival time after LPS challenge, accompanied by alleviated pathology in lung tissues, decreased levels of pro-inflammatory cytokines and altered composition of immune cells in BALF. Furthermore, the transduction of related signaling pathways, including MK5, AKT, JNK, and p38 MAPK pathways, was reduced obviously in LPS-treated MAPK4-/- mice. Notably, the expression of MAPK4 was up-regulated in lung tissues of ALI model, which was not related with MAPK4 promoter methylation, but negatively orchestrated by transcriptional factors NFKB1 and NR3C1. Further studies have shown that the expression of MAPK4 was also increased in LPS-treated macrophages. Meanwhile, MAPK4 deficiency reduced the expression of related pro-inflammatory cytokines in macrophage in response to LPS treatment. Finally, MAPK4 inhibition using shRNA pre-treatment could ameliorate the pathology of lung tissues and prolong the survival time of mice after LPS challenge. Conclusions: Collectively, these findings reveal an important biological function of atypical MAPK in mediating the pathology of ALI, indicating that MAPK4 might be a novel potential therapeutic target for ALI treatment.

scholarly journals Level of pro-inflammatory cytokines in patients with transfusion-related acute lung injury - Multiple comparisons between patients, controls and donor

2019 ◽  
Vol 10 (2) ◽  
pp. 1448-1455
Author(s):  
Adil Shaker Al-Tamimi ◽  
Israa A. Dheeb
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Inflammatory Cytokines ◽  
Case Control Study ◽  
Serum Levels ◽  
Tnf Alpha ◽  
Blood Component ◽  
Ventilator Support ◽  
Control Study ◽  
Pro Inflammatory Cytokines

Transfusion-related acute lung injury recently regarded as the leading cause of death after transfusion. Several pro-inflammatory cytokines TNF, IL6 and IL8 have been linked to the pathogenesis of TRALI, supported by the findings of increased their serum levels in recipient patients. This is a prospective case-control study, twenty-five patients with a diagnosis of TRALI after transfusion of blood products were included and compared to another 25 transfused patients. Serum was obtained after the onset of TRALI in patients and controls. Other samples were obtained from the saved donor transfused bag or segments. All samples were utilized for cytokines assay. The intubation rate among TRALI patients was 48%. No difference was found in the regarding the type of transfusion and the cytokine level for each specific type of blood or blood component transfused between TRALI and controls. The overall TRALI associated mortality was 4%. Results revealed significantly increased TNF alpha IL-6 levels in sera of TRALI patients as compared with control and donor unit for patients with TRALI. Serum levels of IL-8 were significantly higher in patients with TRALI (mean42.11 pg/ml) as compared with sera of control and donor unit for TRALI patients. Serum level of TNF, IL-6 and-8 in patients with TRALI was significantly higher in patients with longer incubation time. Serum cytokines assay in patients with TRALI may add the significant advantage of assessing the severity, associated mortality and predicting the time of ventilator support.

scholarly journals Therapeutic Efficacy of Excretory-Secretory Products of Trichinella spiralis Adult Worms on Sepsis-Induced Acute Lung Injury in a Mouse Model

2021 ◽  
Vol 11 ◽  
Author(s):  
Huihui Li ◽  
Dapeng Qiu ◽  
Huijuan Yang ◽  
Yuan Yuan ◽  
Lingqin Wu ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Therapeutic Effect ◽  
Inflammatory Cytokines ◽  
Lung Tissue ◽  
Therapeutic Efficacy ◽  
Trichinella Spiralis ◽  
Inflammatory Diseases ◽  
Secretory Products ◽  
Pro Inflammatory Cytokines

Acute lung injury (ALI) is a common complication of systemic inflammation or sepsis with high morbidity and mortality. Although many studies have confirmed that helminth-derived proteins had strong immunomodulatory functions and could be used to treat inflammatory diseases, there is no report on the therapeutic effect of excretory-secretory products of Trichinella spiralis adult worms (Ts-AES) on sepsis-induced ALI. In this study, the therapeutic efficacy of Ts-AES on sepsis-induced ALI and the underlying immunological mechanism and the signaling pathway were investigated. The results indicated that after being treated with Ts-AES, the survival rate of mice with CLP-induced sepsis was significantly increased to 50% for 72 hours after CLP surgery compared to PBS control group with all mice died. The sepsis-induced ALI was largely mitigated characterized by reduced inflammation cell infiltration and pathological changes in lung tissue, with decreased lung injury scores and lung wet/dry weight ratio. The therapeutic efficacy of Ts-AES is associated with stimulated Tregs response with increased regulatory cytokines IL-10 and TGF-β and downregulated pro-inflammatory cytokines (TNF-α, IL-6, IL-1β). The expression of HMGB1, TLR2 and MyD88 in lung tissue was inhibited after treatment of Ts-AES. Our results demonstrated that Ts-AES play an important role in immunomodulation and confer a therapeutic effect on sepsis-induced ALI through inhibiting pro-inflammatory cytokines. The activation of Tregs and increased level of regulatory cytokines IL-10 and TGF-β are possibly involved in the immunomodulatory functions of Ts-AES through HMGB1/TLR2/MyD88 signal pathway. The findings suggest Ts-AES is a potential therapeutic agent for prevention and treatment of sepsis-induced ALI and other inflammatory diseases.

Diosmin downregulates the expression of T cell receptors, pro-inflammatory cytokines and NF-κB activation against LPS-induced acute lung injury in mice

2015 ◽  
Vol 102 ◽  
pp. 1-11 ◽  
Author(s):  
Faisal Imam ◽  
Naif O. Al-Harbi ◽  
Mohammed M. Al-Harbi ◽  
Mushtaq Ahmad Ansari ◽  
Khairy M.A. Zoheir ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
T Cell ◽  
Lung Injury ◽  
Inflammatory Cytokines ◽  
T Cell Receptors ◽  
Cell Receptors ◽  
Pro Inflammatory Cytokines

scholarly journals Identification of atypical mitogen-activated protein kinase MAPK4 as a novel regulator in acute lung injury

2020 ◽  
Author(s):  
Ling Mao ◽  
Ya Zhou ◽  
Longqing Chen ◽  
Lin Hu ◽  
Shiming Liu ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Survival Time ◽  
Inflammatory Cytokines ◽  
Mitogen Activated Protein Kinase ◽  
Lps Challenge ◽  
Mitogen Activated Protein ◽  
Pre Treatment ◽  
Pro Inflammatory Cytokines

Abstract Background: Acute lung injury (ALI) is a serious disease with highly morbidity and mortality that causes serious health problems worldwide. Atypical mitogen activated protein kinases (MAPKs) play critical roles in the development of tissues and have been proposed as promising therapeutic targets for various diseases. However, the potential role of atypical MAPKs in ALI remains elusive. In this study, we investigated the role of atypical MAPKs family member MAPK4 in ALI using LPS-induced murine ALI model. Results: We found that MAPK4 deficiency mice exhibited prolonged survival time after LPS challenge, accompanied by alleviated pathology in lung tissues, decreased levels of pro-inflammatory cytokines and altered composition of immune cells in BALF. Furthermore, the transduction of related signaling pathways, including MK5, AKT, JNK, and p38 MAPK pathways, was reduced obviously in LPS-treated MAPK4 -/- mice. Notably, the expression of MAPK4 was up-regulated in lung tissues of ALI model, which was not related with MAPK4 promoter methylation, but negatively orchestrated by transcriptional factors NFKB1 and NR3C1. Further studies have shown that the expression of MAPK4 was also increased in LPS-treated macrophages. Meanwhile, MAPK4 deficiency reduced the expression of related pro-inflammatory cytokines in macrophage in response to LPS treatment. Finally, MAPK4 knockdown using shRNA pre-treatment could ameliorate the pathology of lung tissues and prolong the survival time of mice after LPS challenge. Conclusions: Collectively, these findings reveal an important biological function of atypical MAPK in mediating the pathology of ALI, indicating that MAPK4 might be a novel potential therapeutic target for ALI treatment.

Sign in / Sign up

Export Citation Format

Share Document