Expression of IL-1 and tumor necrosis factor by endothelial cells: role in stimulating fibroblast PGE2 synthesis.

Abstract

We describe the elaboration by endothelial cells of activity that stimulates fibroblast PGE2 production. Culture supernates of human umbilical vein endothelial cells (ECSN) at concentrations of 2.5 to 25% stimulated human foreskin fibroblast PGE2 production 6 to 180-fold. Following molecular sieve chromatography, peak activity eluted with an Mr of 14-18,000. In a standard IL-1 assay, neither ECSN or 14-18,000 Mr fractions possessing PGE2 stimulatory activity were able to stimulate murine thymocyte proliferation in response to PHA. Immunoperoxidase staining of endothelial cells demonstrated intracellular IL-1; after addition of exogenous IL-1 endothelial cells also stained for tumor necrosis factor (TNF). IL-1 and TNF are known to be synergistic in stimulating fibroblast PGE2 synthesis. Thus, elaboration of TNF by endothelial cells may allow detection of IL-1 in fibroblast PGE2 assays when the concentration of IL-1 is inadequate to stimulate thymocyte proliferation. Interactions of cytokines elaborated by cells may play an important role in effects on target cells.