We have proposed previously that the expression of group IIA secretory
phospholipase A(2) (sPLA(2)-IIA), an
enzyme implicated in
inflammation, is under the control of group IVA cytosolic
phospholipase A(2) (cPLA(2)) and 12/15-lipoxygense (12/15-LOX) in
cytokine-stimulated rat fibroblastic 3Y1 cells. Here, we show that the reduction of
cytokine-stimulated sPLA(2)-IIA induction by the cPLA(2) inhibitor
arachidonyl trifluoromethyl ketone (AACOCF(3)) is partially overcome by the addition of various
lysophospholipids, such as
lysophosphatidylcholine (LysoPC). Furthermore, this
lysophospholipid effect was enhanced by further addition of 12/15-LOX products, such as 12(S)- or 15(S)-hydroxyeicosatetraenoic
acid (
HETE) and 13(S)-hydroxyoctadecadienoic
acid (HODE), thus substantiating the hypothesis that the expression of sPLA(2)-IIA is selectively regulated by
lipid products of the cPLA(2)-12/15-LOX pathway. In an attempt to identify a set of 12/15-LOX-regulated genes, the
cDNA subtraction technique, followed by Northern blotting, was performed to screen particular clones, the expression of which was suppressed by the LOX inhibitor
nordihydroguaiaretic acid (NDGA). NDGA-sensitive clones identified thus far included sPLA(2)-IIA, cytoplasmic signaling intermediates, several
oxygenases, extracellular matrices, secretory
proteins, and other cellular
proteins. Of these genes, however, only the expression of sPLA(2)-IIA and 14-3-3eta was enhanced by 12/15-LOX expression. Taken together, our data suggest that sPLA(2)-IIA represents a particular group of genes, the transcription of which is up-regulated by 12/15-LOX metabolites.