Influence of natural and recombinant interleukin 2 on endothelial cell arachidonate metabolism. Induction of de novo synthesis of prostaglandin H synthase
| Autor: | D Seong, H Hatzakis, C M Jones, K Frasier-Scott, Kenneth K. Wu |
|---|---|
| Rok vydání: | 1988 |
| Předmět: |
Interleukin 2
Endothelium Blotting Western Prostacyclin 6-Ketoprostaglandin F1 alpha Arachidonic Acids Cycloheximide Biology Tissue plasminogen activator Umbilical vein Structure-Activity Relationship chemistry.chemical_compound von Willebrand Factor Serine medicine Humans Cysteine Chromatography High Pressure Liquid Alanine Arachidonic Acid General Medicine Epoprostenol Molecular biology Recombinant Proteins Molecular Weight Endothelial stem cell medicine.anatomical_structure Biochemistry chemistry Prostaglandin-Endoperoxide Synthases Enzyme Induction Tissue Plasminogen Activator Dactinomycin cardiovascular system Interleukin-2 Endothelium Vascular Plasminogen activator Research Article medicine.drug |
| Zdroj: | Journal of Clinical Investigation. 82:1877-1883 |
| ISSN: | 0021-9738 |
| DOI: | 10.1172/jci113805 |
| Popis: | We studied the effects of natural and recombinant human IL-2 (rIL-2) on secretion of prostacyclin (PGI2), vWf, and tissue-type plasminogen activator (tPA). IL-2 elicited a steady increase in PGI2 synthesis by cultured human umbilical vein endothelial cells (HUVECS) and bovine aortic endothelial cells but had no effect on vWf or tPA. Both purified natural IL-2 (nIL-2) and rIL-2 induced significant PGI2 synthesis. Substitution of the cysteine residue at position 125 of rIL-2 with serine or alanine led to loss of PGI2-stimulatory activity in HUVECS without affecting thymidine incorporation in lymphocytes. HPLC analysis of arachidonate metabolites detected predominantly 6 keto-PGF1 alpha (6KPGF1 alpha) peak. Treatment of cultured endothelial cells with cycloheximide and actinomycin D resulted in inhibition of 6KPGF1 alpha synthesis. The Western blot using a polyclonal antibody against PGH synthase revealed an increment in the 70-kD subunit of PGH synthase by nIL-2 and rIL-2, but not by alanine-substituted rIL-2. We conclude that IL-2 stimulated sustained PGI2 production by a mechanism that includes the de novo synthesis of PGH synthase. This mechanism for regulating AA metabolism probably has important physiologic implications. |
| Databáze: | OpenAIRE |
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