Interleukin-4 inhibits the gene expression and biosyntheis of cytosolic phospholipase A2 in lipopolysaccharide stimulated U937 macrophage cell line and freshly prepared adherent rheumatoid synovial cells.
We recently reported that interleukin-4 (IL-4) inhibited prostanoid synthesis through inhibiting cyclooxygenase 2 biosynthesis. In the present study, we examined the effect of IL-4 on the expression of cytosolic phospholipase A2 (cPLA2). The amounts of protein and mRNA of cPLA2 were determined by western blotting and reverse transcription polymerase chain reaction (RT-PCR), respectively. Although interleukin-1alpha (IL-1alpha) and tumor necrosis factor alpha (TNFalpha) had little effect on the biosynthesis of cPLA2 in phorbol myristate acetate (PMA)-differentiated U937 cells, lipopolysaccharide (LPS) increased the protein level of cPLA2 in a dose-dependent manner. IL-4 inhibited the increased synthesis of cPLA2 at the mRNA level. In addition, IL-4 inhibited the biosynthesis of cPLA2 in untreated or LPS treated freshly prepared rheumatoid synovial cells at the mRNA level. These findings suggest that IL-4 inhibits prostanoid synthesis through inhibiting the expression of both cPLA2 and cyclooxygenase 2.
Kuroda
A
A
The First Department of Internal Medicine, Toyama Medical and Pharmaceutical University, Sugitani, Japan.
Sugiyama
E
E
Taki
H
H
Mino
T
T
Kobayashi
M
M
D001172:Arthritis, Rheumatoid / Q000201:enzymology* / Q000601:surgery; D002448:Cell Adhesion; D002454:Cell Differentiation; D002460:Cell Line; D003600:Cytosol / Q000201:enzymology; D004790:Enzyme Induction; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D006801:Humans; D015847:Interleukin-4 / Q000494:pharmacology*; D007720:Knee Prosthesis; D008070:Lipopolysaccharides / Q000494:pharmacology*; D016403:Lymphoma, Large B-Cell, Diffuse; D008264:Macrophages / Q000201:enzymology*; D010741:Phospholipases A / Q000096:biosynthesis*; D054467:Phospholipases A2; D016133:Polymerase Chain Reaction; D011994:Recombinant Proteins / Q000494:pharmacology; D013583:Synovial Membrane / Q000201:enzymology* / Q000473:pathology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D008070:Lipopolysaccharides; D011994:Recombinant Proteins; D015847:Interleukin-4; D010741:Phospholipases A; D054467:Phospholipases A2; D013755:Tetradecanoylphorbol Acetate