INTERLEUKIN-4 INHIBITS THE GENE-EXPRESSION AND BIOSYNTHESIS 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 sy nthesis through inhibiting cyclooxygenase 2 biosynthesis. In the prese nt study, we examined the effect of IL-4 on the expression of cytosoli c phospholipase A(2) (cPLA(2)). The amounts of protein and mRNA of cPL A(2) were determined by western blotting and reverse transcription pol ymerase chain reaction (RT-PCR), respectively. Although interleukin-1 alpha (IL-1 alpha) and tumor necrosis factor alpha (TNF alpha) had lit tle effect on the biosynthesis of cPLA(2) in phorbol myristate acetate (PMA)-differentiated U937 cells, lipopolysaccharide (LPS) increased t he protein level of cPLA(2) in a dose-dependent manner. IL-4 inhibited the increased synthesis of cPLA(2) at the mRNA level. In addition, IL -4 inhibited the biosynthesis of cPLA(2) in untreated or LPS treated f reshly prepared rheumatoid synovial cells at the mRNA level. These fin dings suggest that IL-4 inhibits prostanoid synthesis through inhibiti ng the expression of both cPLA(2) and cyclooxygenase 2. (C) 1997 Acade mic Press