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.