Cysteinyl-leukotriene D4 induced IL-1β expression and release in rat vascular smooth muscle cells

Vascular cells, including smooth muscle cells (VSMC), may release interleukin 1 (IL-1) and transcribe its genes for both isoforms. Previous studies have shown that cysteinyl-leukotrienes can modulate cytokine production by monocytes and a cytokine-eicosanoid network has been suggested during atherosclerosis. In this study the effects of cysteinyl-leukotriene D4 (LTD4) on IL-1β production and IL-1β mRNA expression were tested on rat VSMC. LTD4 showed a significant dose-dependent (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-1β immmunoreactivity in the supernatants of conditioned medium and cell lysates. Furthermore, LTD4 induced an increased mRNA expression which began at 1 h and peaked at 12 h incubation time. The production of IL-1β was inhibited by MK-571 (from 145 ± 12 to 60 ± 10 pg/ml), a specific receptor antagonist of LTD4 and partially reduced by IL-1 receptor antagonist (IL-1ra) (from 160 ± 12 to 85 ± 5 pg/ml). These experiments suggest that cysteinyl-leukotrienes, potentially produced in the vascular wall by leukocytes or by trancellular metabolism, may be involved in local IL-1 production. © 1995.