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.

scholarly journals The Disruption of the Endothelial Barrier Contributes to Acute Lung Injury Induced by Coxsackievirus A2 Infection in Mice

2021 ◽  
Vol 22 (18) ◽  
pp. 9895
Author(s):  
Wangquan Ji ◽  
Qiang Hu ◽  
Mengdi Zhang ◽  
Chuwen Zhang ◽  
Chen Chen ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Acute Lung Injury ◽  
Lung Injury ◽  
Pulmonary Edema ◽  
Foot And Mouth Disease ◽  
Epidemiological Studies ◽  
Mapk Signaling ◽  
Lung Damage ◽  
Mitogen Activated Protein Kinase ◽  
Endothelial Barrier

Sporadic occurrences and outbreaks of hand, foot, and mouth disease (HFMD) caused by Coxsackievirus A2 (CVA2) have frequently reported worldwide recently, which pose a great challenge to public health. Epidemiological studies have suggested that the main cause of death in critical patients is pulmonary edema. However, the pathogenesis of this underlying comorbidity remains unclear. In this study, we utilized the 5-day-old BALB/c mouse model of lethal CVA2 infection to evaluate lung damage. We found that the permeability of lung microvascular was significantly increased after CVA2 infection. We also observed the direct infection and apoptosis of lung endothelial cells as well as the destruction of tight junctions between endothelial cells. CVA2 infection led to the degradation of tight junction proteins (e.g., ZO-1, claudin-5, and occludin). The gene transcription levels of von Willebrand factor (vWF), endothelin (ET), thrombomodulin (THBD), granular membrane protein 140 (GMP140), and intercellular cell adhesion molecule-1 (ICAM-1) related to endothelial dysfunction were all significantly increased. Additionally, CVA2 infection induced the increased expression of inflammatory cytokines (IL-6, IL-1β, and MCP-1) and the activation of p38 mitogen-activated protein kinase (MAPK). In conclusion, the disruption of the endothelial barrier contributes to acute lung injury induced by CVA2 infection; targeting p38-MAPK signaling may provide a therapeutic approach for pulmonary edema in critical infections of HFMD.

scholarly journals Store-operated Ca2+ Entry (SOCE) Induced by Protease-activated Receptor-1 Mediates STIM1 Protein Phosphorylation to Inhibit SOCE in Endothelial Cells through AMP-activated Protein Kinase and p38β Mitogen-activated Protein Kinase

2013 ◽  
Vol 288 (23) ◽  
pp. 17030-17041 ◽  
Author(s):  
Premanand C. Sundivakkam ◽  
Viswanathan Natarajan ◽  
Asrar B. Malik ◽  
Chinnaswamy Tiruppathi
Keyword(s):  
Endothelial Cells ◽  
Protein Kinase ◽  
P38 Mapk ◽  
Transient Receptor Potential ◽  
Mapk Signaling ◽  
Mitogen Activated Protein Kinase ◽  
Mouse Lung ◽  
Mitogen Activated Protein ◽  
Protease Activated Receptor 1 ◽  
Amp Activated Protein Kinase

The Ca2+ sensor STIM1 is crucial for activation of store-operated Ca2+ entry (SOCE) through transient receptor potential canonical and Orai channels. STIM1 phosphorylation serves as an “off switch” for SOCE. However, the signaling pathway for STIM1 phosphorylation is unknown. Here, we show that SOCE activates AMP-activated protein kinase (AMPK); its effector p38β mitogen-activated protein kinase (p38β MAPK) phosphorylates STIM1, thus inhibiting SOCE in human lung microvascular endothelial cells. Activation of AMPK using 5-aminoimidazole-4-carboxamide-1-β-d-ribofuranoside (AICAR) resulted in STIM1 phosphorylation on serine residues and prevented protease-activated receptor-1 (PAR-1)-induced Ca2+ entry. Furthermore, AICAR pretreatment blocked PAR-1-induced increase in the permeability of mouse lung microvessels. Activation of SOCE with thrombin caused phosphorylation of isoform α1 but not α2 of the AMPK catalytic subunit. Moreover, knockdown of AMPKα1 augmented SOCE induced by thrombin. Interestingly, SB203580, a selective inhibitor of p38 MAPK, blocked STIM1 phosphorylation and led to sustained STIM1-puncta formation and Ca2+ entry. Of the three p38 MAPK isoforms expressed in endothelial cells, p38β knockdown prevented PAR-1-mediated STIM1 phosphorylation and potentiated SOCE. In addition, inhibition of the SOCE downstream target CaM kinase kinase β (CaMKKβ) or knockdown of AMPKα1 suppressed PAR-1-mediated phosphorylation of p38β and hence STIM1. Thus, our findings demonstrate that SOCE activates CaMKKβ-AMPKα1-p38β MAPK signaling to phosphorylate STIM1, thereby suppressing endothelial SOCE and permeability responses.

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.

scholarly journals APPL1 mediates adiponectin-stimulated p38 MAPK activation by scaffolding the TAK1-MKK3-p38 MAPK pathway

2011 ◽  
Vol 300 (1) ◽  
pp. E103-E110 ◽  
Author(s):  
Xiaoban Xin ◽  
Lijun Zhou ◽  
Caleb M. Reyes ◽  
Feng Liu ◽  
Lily Q. Dong
Keyword(s):  
Protein Kinase ◽  
P38 Mapk ◽  
Mapk Pathway ◽  
Adaptor Protein ◽  
Mapk Signaling ◽  
Mitogen Activated Protein Kinase ◽  
Scaffolding Protein ◽  
Mapk Activation ◽  
P38 Mapk Pathway ◽  
Mitogen Activated Protein

The adaptor protein APPL1 mediates the stimulatory effect of adiponectin on p38 mitogen-activated protein kinase (MAPK) signaling, yet the underlying mechanism remains unclear. Here we show that, in C2C12 cells, overexpression or suppression of APPL1 enhanced or suppressed, respectively, adiponectin-stimulated p38 MAPK upstream kinase cascade, consisting of transforming growth factor-β-activated kinase 1 (TAK1) and mitogen-activated protein kinase kinase 3 (MKK3). In vitro affinity binding and coimmunoprecipitation experiments revealed that TAK1 and MKK3 bind to different regions of APPL1, suggesting that APPL1 functions as a scaffolding protein to facilitate adiponectin-stimulated p38 MAPK activation. Interestingly, suppressing APPL1 had no effect on TNFα-stimulated p38 MAPK phosphorylation in C2C12 myotubes, indicating that the stimulatory effect of APPL1 on p38 MAPK activation is selective. Taken together, our study demonstrated that the TAK1-MKK3 cascade mediates adiponectin signaling and uncovers a scaffolding role of APPL1 in regulating the TAK1-MKK3-p38 MAPK pathway, specifically in response to adiponectin stimulation.

scholarly journals The Expanding Role of p38 Mitogen-Activated Protein Kinase in Programmed Host Cell Death

2019 ◽  
Vol 12 ◽  
pp. 117863611986459 ◽  
Author(s):  
Jessica Gräb ◽  
Jan Rybniker
Keyword(s):  
Protein Kinase ◽  
Host Cell ◽  
P38 Mapk ◽  
Bacterial Infections ◽  
Mapk Signaling ◽  
Mitogen Activated Protein Kinase ◽  
Host Cell Apoptosis ◽  
Mitogen Activated Protein ◽  
P38 Mapk Inhibitors ◽  
Mapk Inhibitors

The p38 mitogen-activated protein kinase (MAPK) is involved in a multitude of essential cellular processes. The kinase is activated in response to environmental stresses, including bacterial infections and inflammation, to regulate the immune response of the host. However, recent studies have demonstrated that pathogens can manipulate p38 MAPK signaling for their own benefit to either prevent or induce host cell apoptosis. In addition, there is evidence demonstrating that p38 MAPK is a potent trigger of pathogen-induced necrosis driven by mitochondrial membrane disruption. Given the large number of p38 MAPK inhibitors that have been tested in clinical trials, these findings provide an opportunity to repurpose these drugs for improved control of infectious diseases.

scholarly journals Weaning Induced Hepatic Oxidative Stress, Apoptosis, and Aminotransferases through MAPK Signaling Pathways in Piglets

2016 ◽  
Vol 2016 ◽  
pp. 1-10 ◽  
Author(s):  
Zhen Luo ◽  
Wei Zhu ◽  
Qi Guo ◽  
Wenli Luo ◽  
Jing Zhang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Signaling Pathways ◽  
Redox Status ◽  
Mapk Signaling ◽  
Mitogen Activated Protein Kinase ◽  
Control Group ◽  
Hepatic Oxidative Stress ◽  
Mitogen Activated Protein ◽  
D 20 ◽  
Mapk Signaling Pathways

This study investigated the effects of weaning on the hepatic redox status, apoptosis, function, and the mitogen-activated protein kinase (MAPK) signaling pathways during the first week after weaning in piglets. A total of 12 litters of piglets were weaned at d 21 and divided into the weaning group (WG) and the control group (CG). Six piglets from each group were slaughtered at d 0 (d 20, referred to weaning), d 1, d 4, and d 7 after weaning. Results showed that weaning significantly increased the concentrations of hepatic free radicals H2O2and NO, malondialdehyde (MDA), and 8-hydroxy-2′-deoxyguanosine (8-OHdG), while significantly decreasing the inhibitory hydroxyl ability (IHA) and glutathione peroxidase (GSH-Px), and altered the level of superoxide dismutase (SOD). The apoptosis results showed that weaning increased the concentrations of caspase-3, caspase-8, caspase-9 and the ratio of Bax/Bcl-2. In addition, aspartate aminotransferase transaminase (AST) and alanine aminotransferase (ALT) in liver homogenates increased after weaning. The phosphorylated JNK and ERK1/2 increased, while the activated p38 initially decreased and then increased. Our results suggested that weaning increased the hepatic oxidative stress and aminotransferases and initiated apoptosis, which may be related to the activated MAPK pathways in postweaning piglets.

p38 MAPK Signaling Mediates Retinoic Acid-Induced Expression of a Novel Tumor Suppressor Protein Programmed Cell Death 4 (PDCD4) in Acute Promyelocytic Leukemia Cells.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 1942-1942
Author(s):  
Ugur Akar ◽  
Bulent Ozpolat ◽  
Nancy Colburn ◽  
Gabriel Lopez-Berestein
Keyword(s):  
Retinoic Acid ◽  
Cell Differentiation ◽  
P38 Mapk ◽  
Myeloid Cell ◽  
Mapk Signaling ◽  
Mitogen Activated Protein Kinase ◽  
Granulocytic Differentiation ◽  
P38 Inhibitor ◽  
Pdcd4 Expression ◽  
Mitogen Activated Protein

Abstract Programmed-cell-death-4 (PDCD4) is a novel tumor suppressor protein that suppresses tumor promoter-induced neoplastic transformation. PDCD4 specifically inhibits the helicase activity of eukaryotic translation initiation factor 4A (eIF4A) and translation initiation and cap-dependent mRNA translation in vitro and in vivo. Loss or underexpression of PDCD4 is associated with carcinogenesis and chemoresistance in solid tumors. The role and regulation of PDCD4 in the the hematopoietic system and myeloid leukemia cells are not known. We previously reported that ATRA induces translational suppression through multiple posttranscriptional mechanisms during terminal cell differentiation (Harris et al, Blood, 104 (5) 2004). Therefore, in this study, we investigated the expression and regulation of PDCD4 during myeloid cell differentiation. All-trans-retinoic acid (ATRA) induces terminal differentiation in acute myeloid leukemia (AML) and promyelocytic (APL) cells, a well established model for myeloid cell differentiation. We found that treatment of HL60 (M2 type AML) and NB4 APL (M3 type AML) cells with ATRA (1 mM) induced PDCD4 protein and mRNA expression during granulocytic differentiation detected by western blot and RT-PCR analysis, respectively. We also demonstrated that inhibition of PDCD4 by siRNA reduced granulocytic differentiation induced by ATRA, suggesting that PDCD4 plays a role in granuliocytic differentiation. To determine mechanisms regulating PDCD4 we investigated the role of pP38 MAPK (Mitogen activated protein kinase) in reugulation of PDCD4 expression. ATRA induced PDCD4 expression correlated with activation of p38 MAPK (Mitogen Activated Protein Kinase) pathway in NB4 cells. To test the hypothesis that p38 MAPK signaling pathway mediates retinoic acid induced PDCD4 expression we treated cells with a specific p38 MAPK inhibitor, SB203580, ATRA or combination with ATRA. We observed that p38 inhibitor inhibited ATRA-induced expression of PDCD4 in NB4 cells. Basal level of PDCD4 expression was also markedly downregulated in the presence of p38 inhibitor when compared to untreated control cells, suggesting that p38 pathway is involved in ATRA-dependent and independent PDCD4 expression. Currently we are investigating whether inhibition of p38 by small interfering RNA (siRNA) will prevent expression of ATRA induced PDCD4 in APL cells. We are also trying to identify whether ATF2 transcription factor, a downstream of p38, is involved in PDCD4 expression. p38-mediated induction of PDCD4 pathway reveals a novel mechanism of PDCD4 regulation and ATRA action, providing a new insight into understanding terminal differentiation of myeloid cells. Better understanding the role of PDCD4 and posttranscriptional control of gene expression may offer targets for the differentiation therapy and chemo preventive strategies.

scholarly journals Activation of PAR4 Induces a Distinct Actin Fiber Formation via p38 MAPK in Human Lung Endothelial Cells

2005 ◽  
Vol 53 (9) ◽  
pp. 1121-1129 ◽  
Author(s):  
Masakazu Fujiwara ◽  
Enjing Jin ◽  
Mohammad Ghazizadeh ◽  
Oichi Kawanami
Keyword(s):  
Endothelial Cells ◽  
P38 Mapk ◽  
Actin Filaments ◽  
Actin Polymerization ◽  
Human Lung ◽  
Mapk Signaling ◽  
Fiber Formation ◽  
Mitogen Activated Protein Kinase ◽  
Actin Fiber ◽  
Lung Endothelial Cells

Protease-activated receptors (PARs) are multifunctional G protein–coupled receptors. Among the four existing PARs, PAR4 is preferentially expressed in the human lung tissue. However, the function of PAR4 has not been defined in the lung endothelial cells. Because PAR1-mediated cellular effects are deeply related to the morphological changes, we focused on the actin fiber and p38 mitogen-activated protein kinase (MAPK) signaling involved in actin polymerization to elucidate the role of PAR4. RT-PCR and Western blot analyses identified PAR4 expression in human pulmonary artery endothelial cells and in human microvascular endothelial cells from lung. We then examined the changes in actin fibers in endothelial cells treated with PAR4-activating peptide. PAR1-activating peptide was used for comparison. Activation of PAR4 and PAR1 by their corresponding peptides induced actin fiber formation; however, the actin filaments were broadly bundled in PAR4 as compared with the ringlike actin filaments in PAR1 activation. Correspondingly, the magnitude of p38 MAPK phosphorylation was different between cells treated with PAR4 and PAR1, with PAR4-activating peptide showing a significantly higher sensitivity to p38 MAPK inhibitor, SB203580. Taken together, these results demonstrate that activation of PAR4 results in the formation of actin fiber distinct from that by PAR1 activation, suggesting PAR4 may play specific roles in the lung endothelial cells.

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