scholarly journals Liver X Receptor Agonist TO901317 Attenuates Paraquat-Induced Acute Lung Injury through Inhibition of NF-κB and JNK/p38 MAPK Signal Pathways

2017 ◽  
Vol 2017 ◽  
pp. 1-13 ◽  
Author(s):  
Xiao Hu ◽  
Haitao Shen ◽  
Yu Wang ◽  
Min Zhao
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Cell Apoptosis ◽  
Interleukin 1 ◽  
Liver X Receptor ◽  
Mitogen Activated Protein Kinase ◽  
Signal Pathways ◽  
Mitogen Activated Protein ◽  
Glutathione S Transferases ◽  
Marked Cell

Paraquat (PQ) is a widely used herbicide with extremely high poisoning mortality mostly from acute lung injury (ALI) or progressive pulmonary fibrosis. Toxicity mechanisms remain unclear, but a redox cycling process that generates reactive oxygen species (ROS) is involved, as are inflammation and cell apoptosis. We established an ALI mouse model by intraperitoneal injection of PQ (28 mg/kg) and then investigated the effects of a potent liver X receptor (LXR) agonist, TO901317 (5 or 20 mg/kg), injected intraperitoneally 30 min after PQ administration. Poisoned mice exhibited severe lung tissue lesions and edema, significant neutrophilic (PMNs) infiltration, and release of the proinflammatory cytokines tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β). PQ administration also decreased activity of antioxidases, including superoxide dismutase (SOD), catalase (CAT), and glutathione S-transferases (GSTs), and increased lipid peroxidation as evaluated by malondialdehyde (MDA) levels. PQ exposure induced upregulation of the proapoptotic gene Bax and downregulation of the antiapoptotic gene Bcl-2, leading to marked cell apoptosis in the lung tissues. TO901317 treatment reversed all these effects through inhibition of PQ-induced nuclear factor kappa B (NF-κB) and JNK/p38 mitogen-activated protein kinase (MAPK) activation. The LXR agonist TO901317 had potent antioxidant, anti-inflammatory, and antiapoptotic effects against PQ-induced 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.

Expression of p38 MAPK in Acute Lung Injury Induced by LPS in Mice

2014 ◽  
Vol 522-524 ◽  
pp. 332-336 ◽  
Author(s):  
Kai Xiu Qin ◽  
Yong Wang ◽  
Hua Gang Jian
Keyword(s):  
Endothelial Cells ◽  
Acute Lung Injury ◽  
Lung Injury ◽  
P38 Mapk ◽  
Inflammatory Cells ◽  
Mapk Signaling ◽  
Mitogen Activated Protein Kinase ◽  
Control Group ◽  
Mitogen Activated Protein ◽  
Set Up

Objective To investigate the expression and roles of p38 mitogen-activated protein kinase (p38 MAPK) in LPS-induced acute lung injury (ALI) in mice. Methods The ALI mice models were set up by intraperineal injection of lipopolysaccharide (LPS). The expressions of p38 MAPK in lung tissues were detected by immunohistochemistry and Western-blot. Results The positive expressions of p38 MAPK distribute mainly in infiltrative inflammatory cells, epithelial cells and endothelial cells. And the level of expression of phosphated p38 MAPK in ALI group were higher obviously than that in the control group, and it reached a peak after two hours. Conclusion p38 MAPK signaling pathway was triggered by ALI induced by endotoxin.

Exosomal MicroRNA-328 from Bone Marrow Mesenchymal Stem Cells (BMSCs) Alleviates Acute Lung Injury Through Mitogen-Activated Protein Kinase/Extracellular Signal-Regulated Kinase (MAPK/ERK) Pathway

2022 ◽  
Vol 12 (2) ◽  
pp. 358-364
Author(s):  
Wei Zhang ◽  
Fang Liu ◽  
Caixia Zhang
Keyword(s):  
Cell Proliferation ◽  
Acute Lung Injury ◽  
Lung Injury ◽  
Cell Damage ◽  
A549 Cells ◽  
Lung Epithelial Cells ◽  
Mitogen Activated Protein Kinase ◽  
Erk Pathway ◽  
Mitogen Activated Protein ◽  
Induced Apoptosis

To elucidate the communication between exosomes (exo) derived from BMSCs and injured lung cells. BMSC-exo was isolated and characterized. Lung epithelial cells A549 were incubated with BMSC-exo, and treated by LPS to induce cell damage. CCK-8 assay was carried out to test cell proliferation, flow cytometry was adopted to analyze cell apoptosis, and RT-qPCR as well as Western blot analysis were selected to assess expression of apoptosis- and anti-apoptosis related proteins. Functional experiment was performed to identify the role of microRNA (miRNA)-328 in lung injury. LPS treatment significantly inhibited the viability of A549 cells, induced apoptosis of A549 cells by increasing Bax and casepase-3 levels and reducing Bcl-2 expression, whilst declined expression of miR-328 and suppressed the phosphorylation activation of the MAPK/ERK pathway. Meanwhile, the amount of IL-6, IL-1β and TNF-α were elevated in injured cells, but, the presence of BMSC-exo eliminated the elevation of the contents. Importantly, treatment with BMSC-exo increased miR-328 expression, activated MAPK MAPK/ERK pathway, inhibited apoptosis, and enhanced cell proliferation. However, the effect of BMSC-exo was attenuated when the cells were silenced for miR-328 expression. Collectively, BMSC-exo enriched miR-328 could relieve acute lung injury through MAPK/ERK pathway.

scholarly journals Mitogen-activated Protein Kinase Kinase Kinase 1 Protects against Nickel-induced Acute Lung Injury

2008 ◽  
Vol 104 (2) ◽  
pp. 405-411 ◽  
Author(s):  
Maureen Mongan ◽  
Zongqing Tan ◽  
Liang Chen ◽  
Zhimin Peng ◽  
Maggie Dietsch ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Protein Kinase ◽  
Lung Injury ◽  
Mitogen Activated Protein Kinase ◽  
Mitogen Activated Protein ◽  
Protein Kinase Kinase

scholarly journals Mitogen-activated protein kinase phosphatase 2, MKP-2, regulates early inflammation in acute lung injury

2012 ◽  
Vol 303 (3) ◽  
pp. L251-L258 ◽  
Author(s):  
Timothy T. Cornell ◽  
Andrew Fleszar ◽  
Walker McHugh ◽  
Neal B. Blatt ◽  
Ann Marie Le Vine ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Protein Kinase ◽  
Lung Injury ◽  
Neutrophil Infiltration ◽  
Mitogen Activated Protein Kinase ◽  
Molecular Response ◽  
Proinflammatory Response ◽  
Mapk Pathways ◽  
Mitogen Activated Protein

Acute lung injury (ALI) is mediated by an early proinflammatory response resulting from either a direct or indirect insult to the lung mediating neutrophil infiltration and consequent disruption of the alveolar capillary membrane ultimately leading to refractory hypoxemia. The mitogen-activated protein kinase (MAPK) pathways are a key component of the molecular response activated by those insults triggering the proinflammatory response in ALI. The MAPK pathways are counterbalanced by a set of dual-specific phosphatases (DUSP) that deactivate the kinases by removing phosphate groups from tyrosine or threonine residues. We have previously shown that one DUSP, MKP-2, regulates the MAPK pathway in a model of sepsis-induced inflammation; however, the role of MKP-2 in modulating the inflammatory response in ALI has not been previously investigated. We utilized both MKP-2-null (MKP-2−/−) mice and MKP-2 knockdown in a murine macrophage cell line to elucidate the role of MKP-2 in regulating inflammation during ALI. Our data demonstrated attenuated proinflammatory cytokine production as well as decreased neutrophil infiltration in the lungs of MKP-2−/− mice following direct, intratracheal LPS. Importantly, when challenged with a viable pathogen, this decrease in neutrophil infiltration did not impact the ability of MKP-2−/− mice to clear either gram-positive or gram-negative bacteria. Furthermore, MKP-2 knockdown led to an attenuated proinflammatory response and was associated with an increase in phosphorylation of ERK and induction of a related DUSP, MKP-1. These data suggest that altering MKP-2 activity may have therapeutic potential to reduce lung inflammation in ALI without impacting pathogen clearance.

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.

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