Interleukin-1 stimulates prostacyclin production by cultured human endothelial cells by increasing arachidonic acid mobilization and conversion.

Abstract

lnterieukln-1 (IL-1) induced slow, lasting activation of human endothelial cells (EC) to release prostacyclin (PGI 2 ). This was accompanied by endogenous3 H-arachldonlc acid f H-AA) release and by a time-dependent Increase In the cells' ability to convert exogenous AA. The continuous presence of IL-1 was not required, but about a 1-hour stimulation with the cytoklne was sufficient to trigger the cells to synthesize PGI 2 for several hours. The spectrum of 3 H-AA conversion shows that, In addition to 6-ketoprostaglandln F 1a , prostaglandln F^, also was raised after IL-1. The recovery of PGI 2 synthesis after aspirin was faster In IL-1-treated EC than In control cells. These data define some of the characteristics of IL-1 stimulation of PGI 2 and suggest that this process Is mediated both by endogenous AA mobilization and by an increase In cyclooxygenase activity. (Arteriosclerosis 10:129-134, January/February 1990) P rostacyclin (PGy is an important biosynthetic product of endothelial cells (EC). It inhibits platelet aggregation and thrombus formation and acts as a potent vasodilator by causing relaxation in vascular smooth muscle cells.1 PGI 2 hatf-life, when released into the circulation, is in the range of a few minutes, and its activity on platelets and vascular tone is extremely short lived. 1 Therefore, its biological relevance in vivo is strictly related to "how much and for how long" it can be produced by the vessel wall.Most known activators, e.g., thrombin, bradykinin, or ionophore A23187, induce a very fast, short-lasting release of PGI 2 by EC, followed by cell refractoriness to subsequent stimulation.2 ' 3 We and other groups have shown that the immunomediator, interieukin-1 (IL-1), has a peculiar way of inducing PGI 2 synthesis in EC.45 IL-1 stimulation requires a few hours to become apparent, but then it lasts for several hours.IL-1 is probably one of the most important mediators of the hemodynamic and hematological changes characteristic of septic shock.6 ' 7 The hemodynamic alterations, particularly the hypotension caused by IL-1, require cyclooxygenase products, since they are reversed by inhibitors of this enzyme.7 It has, therefore, been hypothesized that PGI 2 synthesis by EC plays an important role in mediating the slow and lasting drop in systemic vascular resistance that follows IL-1 release in the circulation. Despite its biological importance, little is known about the mechanism and the pattern through which IL-1 exerts its stimulatory activity on EC. In this work, we report that IL-1 induces endogenous arachidonic add (AA) mobilization and increases its conversion to prostaglandins via an increase in cyclooxygenase synthesis and activity. This effect is long lasting but does not need the continuous presence of IL-1 to be apparent. Methods Endothelial Cell CultureEC were isolated from human umbilical vein and cultured in medium 199 supplemented with 20% newborn calf serum as previously described in detail.2 The cells were used at the first passage at confluence, and they were maintaine...

Rate of Vasoconstrictor Prostanoids Released by Endothelial Cells Depends on Cyclooxygenase-2 Expression and Prostaglandin I Synthase Activity

“…In agreement with other reports, 16,33,34,36,46 we observed that release of PGI 2 by HUVECs was increased in cells exposed to IL-1␤ compared with resting cells. However, the release of PGF 2␣ and PGE 2 was substantially more induced by IL-1␤ than was the release of PGI 2 .…”

The role IL-1 in tumor-mediated angiogenesis

“…Nevertheless, it is not known whether the described effects of IL-1 on ECs are direct, due to its action, or indirect, due to IL-1-induced cytokines produced by ECs. It was found that in vitro , IL-1β increases expression of FGF2 in ECs through activation of NF-κB (Lee and Kay, 2012) and also induces expression of different chemokines, cytokines, direct angiogenic factors, and adhesion molecules on ECs (Breviario et al, 1990; Sica et al, 1990; Kang et al, 2006). In addition, IL-1β interaction with IL-1R1 on ECs induces migration of the cells and tube formation, mainly via activation of p38-mitogen-activated protein kinase (MAPK) and MAPK-activated protein kinase 2 (Jagielska et al, 2012).…”

Interaction of vasculotropin/vascular endothelial cell growth factor with human umbilical vein endothelial cells: Binding, internalization, degradation, and biological effects

“…In addition, we have looked into the putative role of VASIVEGF on prostacyclin production and tissue factor expression, since, beside their role in angiogenesis, endothelial cells respond to various cytokines by increasing both of these activities (Bevilacqua et al, 1984(Bevilacqua et al, , 1986Brevario et al, 1990;Zavoico et al, 1990).…”