CYSTEINYL-LEUKOTRIENE D-4 INDUCED IL-1-BETA EXPRESSION AND RELEASE INRAT VASCULAR SMOOTH-MUSCLE CELLS

Vascular cells, including smooth muscle cells (VSMC), may release inte rleukin 1 (IL-1) and transcribe its genes for both isoforms. Previous studies have shown that cysteinyl-leukotrienes can modulate cytokine p roduction by monocytes and a cytokine-eicosanoid network has been sugg ested during atherosclerosis. In this study the effects of cysteinyl-l eukotriene D-4 (LTD(4)) on IL-1 beta production and IL-1 beta mRNA exp ression were tested on rat VSMC. LTD(4) showed a significant dose-depe ndent (from basal production of 55 +/- 15 pg/ml to maximal production of 177 +/- 14 pg/ml) and time-dependent (peaking at 24 h 16 +/- 54 pg/ ml) increase of IL-1 beta immmunoreactivity in the supernatants of con ditioned medium and cell lysates. Furthermore, LTD, induced an increas ed mRNA expression which began at 1 h and peaked at 12 h incubation ti me. The production of IL-1 beta was inhibited by MK-571 (from 145 +/- 12 to 60 +/- 10 pg/ml), a specific receptor antagonist of LTD, and par tially reduced by IL-1 receptor antagonist (IL-1ra) (from 160 +/- 12 t o 85 +/- 5 pg/ml). These experiments suggest that cysteinyl-leukotrien es, potentially produced in the vascular wall by leukocytes or by tran cellular metabolism, may be involved in local IL-1 production.