Cytosolic phospholipase A2 Group IValpha but not secreted phospholipase A2 Group IIA, V, or X induces interleukin-8 and cyclooxygenase-2 gene and protein expression through peroxisome proliferator-activated receptors gamma 1 and 2 in human lung cells

Autor: Marek L. Kowalski, Marion G. Lawrence, James H. Shelhamer, Carolea Logun, Tong Wu, Anetta Ptasinska, Grzegorz Woszczek, Rafał Pawliczak, Patricia Madara
Rok vydání: 2004
Předmět:
Time Factors
Immunoblotting
Peroxisome proliferator-activated receptor
Transfection
Biochemistry
Group II Phospholipases A2
Phospholipases A
Group V Phospholipases A2
Phospholipase A2
Cytosol
Epidermal growth factor
Genes
Reporter
Cell Line
Tumor
Gene expression
Group X Phospholipases A2
Humans
Interleukin 8
RNA
Messenger
RNA
Small Interfering
Receptor
Molecular Biology
Lung
Calcimycin
chemistry.chemical_classification
Cell Nucleus
Messenger RNA
Reporter gene
Arachidonic Acid
biology
Epidermal Growth Factor
Ionophores
Reverse Transcriptase Polymerase Chain Reaction
Group IV Phospholipases A2
Interleukin-8
Membrane Proteins
Cell Biology
Molecular biology
Isoenzymes
PPAR gamma
Phospholipases A2
chemistry
Gene Expression Regulation
Cyclooxygenase 2
Phospholipases
Prostaglandin-Endoperoxide Synthases
biology.protein
RNA
Plasmids
Zdroj: The Journal of biological chemistry. 279(47)
ISSN: 0021-9258
Popis: It has been reported that interleukin-8 (IL-8) and cyclooxygenase-2 (COX-2) expression is regulated by peroxisome proliferator-activated receptor (PPAR)-gamma synthetic ligands. We have shown previously that cytosolic phospholipase A2 (cPLA2) is able to activate gene expression through PPAR-gamma response elements (Pawliczak, R., Han, C., Huang, X. L., Demetris, A. J., Shelhamer, J. H., and Wu, T. (2002) J. Biol. Chem. 277, 33153-33163). In this study we investigated the influence of cPLA2 and secreted phospholipase A2 (sPLA2) Group IIA, Group V, and Group X on IL-8 and COX-2 expression in human lung epithelial cells (A549 cells). We also studied the results of cPLA2 activation by epidermal growth factor (EGF) and calcium ionophore (A23187) on IL-8 and COX-2 reporter gene activity, mRNA level, and protein synthesis. cPLA2 overexpression and activation increased both IL-8 and COX-2 reporter gene activity. Overexpression and activation of Group IIA, Group V, or Group X sPLA2s did not increase IL-8 and COX-2 reporter gene activity. Methyl arachidonyl fluorophosphate, a cPLA2 inhibitor, inhibited the effect of A23187 and of EGF on both IL-8 and COX-2 reporter gene activity, steady state levels of IL-8 and COX-2 mRNA, and IL-8 and COX-2 protein expression. Small inhibitory RNAs directed against PPAR-gamma1 and -gamma2 blunted the effect of A23187 and of EGF on IL-8 and COX-2 protein expression. Moreover small inhibitory RNAs directed against cPLA2 decreased the effect of A23187 and EGF on IL-8 and COX-2 protein expression. These results demonstrate that cPLA2 has an influence on IL-8 and COX 2 gene and protein expression at least in part through PPAR-gamma.
Databáze: OpenAIRE
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