Interleukin-1 beta-induced type IIA secreted phospholipase A(2) geneexpression and extracellular activity in rat vascular endothelial cells

摘要

Two phospholipase A(2) (PLA(2)) isoforms, secretory and cytosolic, have been implicated in inflammation. Secretory type IIA PLA(2) (sPLA(2)-IIA), which hydrolyzes fatty acids bound at the sn-2 position of glycerophospholipids, has been detected universally in a variety of mammalian tissues and cells. The expression of the sPLA(2)-IIA gene and its extracellular activity were shown to be regulated by different factors such as hypoxia, cytokines and phorbol esters. In the present study, we examined the effects of interleukin-1 beta (IL-1 beta) on the expression of the 14 kDa sPLA(2)-IIA, determined using reverse transcription polymerase chain reaction and radiometric Escherichia coli enzyme assay in primary cultures of rat endothelial cells and in two different rat endothelial cell lines (SVAREC and RBE4). These experiments revealed that IL-1 beta induces sPLA(2)IIa gene expression and secretion of the enzyme in endothelial cells in a dose- and time-dependent manner. The cAMP-elevator forskolin did not augment the cytokine-induced elevation of sPLA(2)-IIa enzyme activity but significantly increased the IL-1 beta -stimulated sPLA(2)-IIa mRNA contents in endothelial cells.