07 August 2010
Cytosolic phospholipase A2 group IVA influence on GM-CSF expression in human lung cells: A pilot studyMilena SokolowskaABCDEFG, Joanna StefanskaBDE, Karolina Wodz-NaskiewiczB, Rafal PawliczakACDEFG
Med Sci Monit 2010; 16(9): BR300-306 :: ID: 881121
Background: Granulocyte-macrophage colony-stimulating factor (GM-CSF) is an important mediator in the differentiation, maturation, and survival of inflammatory cells. It might play a significant role in the pathogenesis of asthma. We have shown previously that cytosolic phospholipase A2 group IV A (cPLA2α) is able to activate gene expression, through peroxisome proliferator-activated receptor (PPAR)-γ response elements (PPRE). In the promoter regions of GM-CSF gene (CSF2), we have found potential PPRE. The goal of the current study was to investigate the influence of cPLA2 overexpression and activation on CSF2 gene expression in human lung cells.
Material/Methods: Subconfluent A549 cells were transfected with GM-CSF reporter gene and cPLA2α overexpression vector. Transfected cells were treated with or without calcium ionophore, A23187, or epidermal growth factor (EGF). Cell lysates were collected and assayed for dual luciferase activity. Some cultures were preincubated with a potent cPLA2α inhibitor, methyl arachidonyl fluorophosphonate (MAFP); a secretory phospholipase A2 inhibitor, thioetheramide-PC; a calcium-independent phospholipase A2 inhibitor, bromoenol lactone (BEL); or vehicle. After preincubation, cells were treated with A23187. Expression of GM-CSF messenger RNA (mRNA) was measured using real-time polymerase chain reaction mRNA quantification.
Results: Overexpression of cPLA2α or activation of endogenous cPLA2α by calcium ionophore or EGF caused a significant increase in GM-CSF relative luciferase activity. Calcium ionophore significantly increased GM-CSF mRNA in A549 human lung cells. These effects were at least in part inhibited by MAFP treatment, but not by BEL or thioetheramide-PC.
Conclusions: These preliminary data might suggest an influence of cPLA2α on GM-CSF gene expression in human lung cells, which could play a role in the pathogenesis of asthma and other inflammatory diseases.
Keywords: Lung - pathology, Group IV Phospholipases A2 - physiology, Granulocyte-Macrophage Colony-Stimulating Factor - metabolism, Genes, Reporter, Gene Expression Regulation, Neoplastic - drug effects, Epidermal Growth Factor - pharmacology, Enzyme Inhibitors - pharmacology, Animals, Lung Neoplasms - pathology, Pilot Projects, Rats, Time Factors
01 November 2021 : EditorialEditorial: What Can be Learned from National and International Vaccine Adverse Event Reporting Systems During the COVID-19 Pandemic?
Med Sci Monit 2022; 28:e935299
26 November 2021 : EditorialEditorial: SARS-CoV-2 Vaccine Responses and Breakthrough COVID-19
Med Sci Monit In Press; DOI: 10.12659/MSM.935624
08 November 2021 : Database AnalysisVirtual Screening and Molecular Docking to Study the Mechanism of Chinese Medicines in the Treatment of Cor...
Med Sci Monit In Press; DOI: 10.12659/MSM.934102
01 November 2021 : EditorialEditorial: What Can be Learned from National and International Vaccine Adverse Event Reporting Systems Duri...
Med Sci Monit 2022; 28:e935299
29 Nov 2021 : Database AnalysisIntegrated Analysis of Angiogenesis-Mediated Tumor Immune Microenvironment Pattern in Hepatocellular Carcin...
Med Sci Monit In Press; DOI: 10.12659/MSM.934937
26 Nov 2021 : Clinical ResearchSerum Uric Acid Levels in Relation to Atrial Fibrillation: A Case-Control Study
Med Sci Monit In Press; DOI: 10.12659/MSM.934007
26 Nov 2021 : Database AnalysisNetwork Pharmacology Integrated Molecular Docking Revealed the Mechanism of Jianpi Yiqi Taohua Decoction Ag...
Med Sci Monit In Press; DOI: 10.12659/MSM.933537
Most Viewed Current Articles
20 Mar 2020 : Clinical ResearchSocial Capital and Sleep Quality in Individuals Who Self-Isolated for 14 Days During the Coronavirus Diseas...
Med Sci Monit 2020; 26:e923921
15 Apr 2020 : Clinical ResearchPsychological Impact and Coping Strategies of Frontline Medical Staff in Hunan Between January and March 20...
Med Sci Monit 2020; 26:e924171
05 May 2020 : Review articleAn Evidence Based Perspective on mRNA-SARS-CoV-2 Vaccine Development
Med Sci Monit 2020; 26:e924700