The Co-Ordinate Regulation of Lipocortin 1, Cox 2 and CPLA2 by IL-1β in A549 Cells

1997 ◽  
pp. 249-253 ◽  
Author(s):  
S. P. Newman ◽  
J. D. Croxtall ◽  
Q. Choudhury ◽  
R. J. Flower
Keyword(s):  
A549 Cells ◽  
Cox 2

Isoflurane Regulates Atypical Type-A γ-Aminobutyric Acid Receptors in Alveolar Type II Epithelial Cells

2013 ◽  
Vol 118 (5) ◽  
pp. 1065-1075 ◽  
Author(s):  
Yun-Yan Xiang ◽  
Xuanmao Chen ◽  
Jingxin Li ◽  
Shuanglian Wang ◽  
Gil Faclier ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Gabaa Receptor ◽  
Gabaa Receptors ◽  
Human Lung ◽  
A549 Cells ◽  
Volatile Anesthetics ◽  
Aminobutyric Acid ◽  
Alveolar Type ◽  
Type Ii ◽  
Cox 2

Abstract Background: Volatile anesthetics act primarily through upregulating the activity of γ-aminobutyric acid type A (GABAA) receptors. They also exhibit antiinflammatory actions in the lung. Rodent alveolar type II (ATII) epithelial cells express GABAA receptors and the inflammatory factor cyclooxygenase-2 (COX-2). The goal of this study was to determine whether human ATII cells also express GABAA receptors and whether volatile anesthetics upregulate GABAA receptor activity, thereby reducing the expression of COX-2 in ATII cells. Methods: The expression of GABAA receptor subunits and COX-2 in ATII cells of human lung tissue and in the human ATII cell line A549 was studied with immunostaining and immunoblot analyses. Patch clamp recordings were used to study the functional and pharmacological properties of GABAA receptors in cultured A549 cells. Results: ATII cells in human lungs and cultured A549 cells expressed GABAA receptor subunits and COX-2. GABA induced currents in A549 cells, with half-maximal effective concentration of 2.5 µm. Isoflurane (0.1–250 µm) enhanced the GABA currents, which were partially inhibited by bicuculline. Treating A549 cells with muscimol or with isoflurane (250 µm) reduced the expression of COX-2, an effect that was attenuated by cotreatment with bicuculline. Conclusions: GABAA receptors expressed by human ATII cells differ pharmacologically from those in neurons, exhibiting a higher affinity for GABA and lower sensitivity to bicuculline. Clinically relevant concentrations of isoflurane increased the activity of GABAA receptors and reduced the expression of COX-2 in ATII cells. These findings reveal a novel mechanism that could contribute to the antiinflammatory effect of isoflurane in the human lung.

scholarly journals MicroRNA-381 Negatively Regulates TLR4 Signaling in A549 Cells in Response to LPS Stimulation

2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Zhihao Xu ◽  
Dapeng Dong ◽  
Xiaofei Chen ◽  
Huaqiong Huang ◽  
Shenglan Wen
Keyword(s):  
Target Gene ◽  
Target Genes ◽  
Bioinformatics Analysis ◽  
Respiratory Infections ◽  
A549 Cells ◽  
Luciferase Reporter ◽  
Reporter Assay ◽  
Elisa Kit ◽  
Cox 2

It is widely reported that miR-381 is dysregulated in various tumors. However, the specific role of miR-381 in respiratory infections has not been reported. To probe this role, A549 cells were pretreated with 1 μg/mL LPS for 24 h. The level of miR-381 was detected using RT-qPCR. The expression of proinflammatory cytokines was determined using an ELISA kit and western blotting. Bioinformatics analysis was used to predict the target genes of miR-381, and a luciferase reporter assay was used to validate the expression of the target genes. miR-381 expression was increased in A549 cells treated with LPS, which is a ligand of TLRs. Further study revealed that the overexpression of miR-381 increased the activity of NF-κB signaling, thereby increasing the expression of IL-6, TNFα, and COX-2. Further study revealed that IκBα was a target gene of miR-381. The upregulation of miR-381 under LPS stimulation contributes to respiratory infections mainly by targeting IκBα.

scholarly journals Glucosamine Hydrochloride Specifically Inhibits COX-2 by Preventing COX-2 N-Glycosylation and by Increasing COX-2 Protein Turnover in a Proteasome-dependent Manner

2007 ◽  
Vol 282 (38) ◽  
pp. 27622-27632 ◽  
Author(s):  
Byeong-Churl Jang ◽  
Su-Haeng Sung ◽  
Jong-Gu Park ◽  
Jong-Wook Park ◽  
Jae Hoon Bae ◽  
...  
Keyword(s):  
Molecular Mass ◽  
Protein Turnover ◽  
A549 Cells ◽  
Lung Epithelial Cells ◽  
Prostaglandin E ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Glucosamine Hydrochloride ◽  
Cox 2 ◽  
Factor Α

COX-2 and its products, including prostaglandin E2, are involved in many inflammatory processes. Glucosamine (GS) is an amino monosaccharide and has been widely used for alternative regimen of (osteo) arthritis. However, the mechanism of action of GS on COX-2 expression remains unclear. Here we describe a new action mechanism of glucosamine hydrochloride (GS-HCl) to tackle endogenous and agonistdriven COX-2 at protein level. GS-HCl (but not GS sulfate, N-acetyl GS, or galactosamine HCl) resulted in a shift in the molecular mass of COX-2 from 72–74 to 66–70 kDa and concomitant inhibition of prostaglandin E2 production in a concentration-dependent manner in interleukin (IL)-1β-treated A549 human lung epithelial cells. Remarkably, GS-HCl-mediated decrease in COX-2 molecular mass was associated with inhibition of COX-2 N-glycosylation during translation, as assessed by the effect of tunicamycin, the protein N-glycosylation inhibitor, or of cycloheximide, the translation inhibitor, on COX-2 modification. Specifically, the effect of low concentration of GS-HCl (1 mm) or of tunicamycin (0.1 μg/ml) to produce the aglycosylated COX-2 was rescued by the proteasomal inhibitor MG132 but not by the lysosomal or caspase inhibitors. However, the proteasomal inhibitors did not show an effect at 5 mm GS-HCl, which produced the aglycosylated or completely deglycosylated form of COX-2. Notably, GS-HCl (5 mm) also facilitated degradation of the higher molecular species of COX-2 in IL-1β-treated A549 cells that was retarded by MG132. GS-HCl (5 mm) was also able to decrease the molecular mass of endogenous and IL-1β- or tumor necrosis factor-α-driven COX-2 in different human cell lines, including Hep2 (bronchial) and H292 (laryngeal). However, GS-HCl did not affect COX-1 protein expression. These results demonstrate for the first time that GS-HCl inhibits COX-2 activity by preventing COX-2 co-translational N-glycosylation and by facilitating COX-2 protein turnover during translation in a proteasome-dependent manner.

Bradykinin increases IL-8 generation in airway epithelial cells via COX-2-derived prostanoids

2002 ◽  
Vol 283 (3) ◽  
pp. L612-L618 ◽  
Author(s):  
Helen C. Rodgers ◽  
Linhua Pang ◽  
Elaine Holland ◽  
Lisa Corbett ◽  
Simon Range ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Epithelial Cells ◽  
A549 Cells ◽  
Airway Epithelial Cells ◽  
Prostaglandin E ◽  
Airway Epithelial ◽  
Neutrophilic Inflammation ◽  
Airway Diseases ◽  
Cox Inhibitor ◽  
Cox 2

Interleukin (IL)-8, the C-X-C chemokine, is a potent neutrophil chemoattractant that has been implicated in a number of inflammatory airway diseases such as cystic fibrosis. Here we tested the hypothesis that bradykinin, an inflammatory mediator and chloride secretagogue, would increase IL-8 generation in airway epithelial cells through autocrine generation of endogenous prostanoids. Bradykinin increased IL-8 generation in both a non-cystic fibrosis (A549) and cystic fibrosis epithelial cell line (CFTE29[Formula: see text]) that was inhibited by the nonselective cyclooxygenase (COX) inhibitor indomethacin and the COX-2 selective inhibitor NS-398. COX-2 was the only isoform of COX expressed in both cell lines. Furthermore, the COX substrate arachidonic acid and exogenous prostaglandin E2 both increased IL-8 release in A549 cells. These results suggest that bradykinin may contribute to neutrophilic inflammation in the airway by generation of IL-8 from airway epithelial cells. The dependence of this response on endogenous production of prostanoids by COX-2 suggests that selective COX-2 inhibitors may have a role in the treatment of airway diseases characterized by neutrophilic inflammation such as cystic fibrosis or chronic obstructive pulmonary disease.

scholarly journals ATPγS stimulates COX‐2 expression via p38 and p42/p44 MAPK in A549 cells

2008 ◽  
Vol 22 (S1) ◽  
Author(s):  
Wan‐Ling Wu ◽  
Chuen‐Mao Yang
Keyword(s):  
A549 Cells ◽  
Cox 2

scholarly journals Impaired COX‐2/PGE2‐mediated anti‐viral response in G6PDknockdown A549 cells through NOX/MAPK signaling

2013 ◽  
Vol 27 (S1) ◽  
Author(s):  
Hsin Ru Lin ◽  
Yi Hsuan Wu ◽  
Chuen Mao Yang ◽  
Daniel Tsun Yee Chiu
Keyword(s):  
A549 Cells ◽  
Mapk Signaling ◽  
Viral Response ◽  
Cox 2

scholarly journals Resveratrol inhibits the proliferation of A549 cells by inhibiting the expression of COX-2

2018 ◽  
Vol Volume 11 ◽  
pp. 2981-2989 ◽  
Author(s):  
Xia Li ◽  
Fang Li ◽  
Fangfang Wang ◽  
Jinfeng Li ◽  
Cunzhi Lin ◽  
...  
Keyword(s):  
A549 Cells ◽  
Cox 2

Interactions between neutrophils and NSCLC cells in vitro effects on neutrophil inflammatory mediator generation and tumour cell proliferation

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e22148-e22148
Author(s):  
K. Hattar ◽  
K. Franz ◽  
M. Ludwig ◽  
A. Banat ◽  
W. Seeger ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Tumour Cell ◽  
Respiratory Burst ◽  
A549 Cells ◽  
Specific Inhibitor ◽  
Human Neutrophils ◽  
Dependent Manner ◽  
Cox 2 ◽  
Tumour Cell Proliferation ◽  
Neutrophil Respiratory Burst

e22148 Background: Growing evidence indicates that interactions between tumour cells and the inflammatory cellular microenvironment are crucial for tumour biology. In NSCLC, both bacterial infections and leukocytosis are associated with a poor prognosis. Against this background, we studied the effect of normal bronchial epithelial cells (B2B) and NSCLC cells (A549) on inflammatory neutrophil behaviour and quantified tumour cell proliferation in the presence of neutrophils. Methods: Isolated human neutrophils were co-cultured with B2B or A549 cells. Neutrophil respiratory burst was quantified by cytochrome C reduction and elastase activity was measured by the kinetics of substrate turnover. Proliferation of A549 cells was determined by MTS- assay. Results: Co-culturing human neutrophils with A549 cells stimulated neutrophil respiratory burst and degranulation in response to the bacterial tripeptide fMLP. In contrast, when co-cultured with B2B cells, these inflammatory neutrophil reactions were blunted. This could be attributed to release of NO and adenosine by the B2B cells. The increase of oxygen radical release and elastase degranulation in the presence of A549 cells was mediated by direct cell-to-cell contact. COX-2 dependent prostanoids were obviously involved in the activation of inflammatory neutrophil behaviour, as shown by the inhibitory capacity of the COX-2 specific inhibitor NS-398 in the co-culture system. Interestingly, activated neutrophils induced proliferation of NSCLC cells in a dose-dependent manner. Conclusions: The reciprocal interactions between neutrophils and NSCLC cells may enhance neutrophil-derived tissue destruction and tumour growth under inflammatory conditions. No significant financial relationships to disclose.

Adenosine triphosphate regulates NADPH oxidase activity leading to hydrogen peroxide production and COX-2/PGE2 expression in A549 cells

2012 ◽  
Vol 303 (5) ◽  
pp. L401-L412 ◽  
Author(s):  
Chih-Chung Lin ◽  
I-Ta Lee ◽  
Wan-Ling Wu ◽  
Wei-Ning Lin ◽  
Chuen-Mao Yang
Keyword(s):  
Nadph Oxidase ◽  
A549 Cells ◽  
Extracellular Nucleotides ◽  
Enzyme Linked Immunosorbent Assay ◽  
Ros Generation ◽  
Prostaglandin E ◽  
Human Beings ◽  
Cell Lung Carcinoma ◽  
Promoter Assay ◽  
Cox 2

Non-small cell lung carcinoma (NSCLC) accounts for most of all lung cancers, which is the leading cause of mortality in human beings. High level of cyclooxygenase-2 (COX-2) is one of the features of NSCLC and related to the low survival rate of NSCLC. However, whether extracellular nucleotides releasing from stressed resident tissues contributes to the expression of COX-2 remains unclear. Here, we showed that stimulation of A549 cells by adenosine 5′- O-(3-thiotriphosphate) (ATPγS) led to an increase in COX-2 gene expression and prostaglandin E2 (PGE2) synthesis, revealed by Western blotting, RT-PCR, promoter assay, and enzyme-linked immunosorbent assay. In addition, ATPγS induced intracellular reactive oxygen species (ROS) generation through the activation of NADPH oxidase. The increase of ROS level resulted in activation of the c-Src/epidermal growth factor receptor (EGFR)/phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)/nuclear factor (NF)-κB cascade. We also found that activated Akt was translocated into the nucleus and recruited with NF-κB and p300 to form a complex. Thus, activation of p300 modulated the acetylation of histone H4 via the NADPH oxidase/c-Src/EGFR/PI3K/Akt/NF-κB cascade stimulated by ATPγS. Our results are the first to show a novel role of NADPH oxidase-dependent Akt/p65/p300 complex formation that plays a key role in regulating COX-2/PGE2 expression in ATPγS-treated A549 cells. Taken together, we demonstrated that ATPγS stimulated activation of NADPH oxidase, resulting in generation of ROS, which then activated the downstream c-Src/EGFR/PI3K/Akt/NF-κB/p300 cascade to regulate the expression of COX-2 and synthesis of PGE2 in A549 cells. Understanding the regulation of COX-2 expression and PGE2 release by ATPγS on A549 cells may provide potential therapeutic targets of NSCLC.

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