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

Atherosclerosis. 1995 Jun;115(2):181-9. doi: 10.1016/0021-9150(94)05510-p.

Abstract

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-1 beta production and IL-1 beta 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-1 beta immunoreactivity 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-1 beta 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-1 ra) (from 160 +/- 12 to 85 +/- 5 pg/ml). These experiments suggest that cysteinyl-leukotrienes, potentially produced in the vascular wall by leukocytes or by transcellular metabolism, may be involved in local IL-1 production.

MeSH terms

  • Analysis of Variance
  • Animals
  • Aorta / cytology
  • Aorta / drug effects
  • Aorta / metabolism
  • Cells, Cultured
  • Dose-Response Relationship, Drug
  • Gene Expression Regulation / drug effects
  • Interleukin-1 / biosynthesis*
  • Interleukin-1 / genetics
  • Interleukin-1 / metabolism
  • Leukotriene D4 / pharmacology*
  • Muscle, Smooth, Vascular / cytology
  • Muscle, Smooth, Vascular / drug effects*
  • Muscle, Smooth, Vascular / metabolism
  • Propionates / pharmacology
  • Quinolines / pharmacology
  • RNA, Messenger / drug effects
  • RNA, Messenger / metabolism
  • Rats
  • Receptors, Interleukin-1 / antagonists & inhibitors

Substances

  • Interleukin-1
  • Propionates
  • Quinolines
  • RNA, Messenger
  • Receptors, Interleukin-1
  • verlukast
  • Leukotriene D4