Functional antagonism between IL-2 and PGA1 or PGJ2 in the control of proliferation of human cord blood-derived mononuclear cells

• Published in: International journal of immunopharmacology Vol. 18; no. 11; pp. 609 - 622
• Main Authors: FRANZESE, O, BONMASSAR, E, MARCUCCI, A, D'ONOFRIO, C
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Science 01.11.1996
• Subjects: Antineoplastic agents; Antineoplastic Agents - pharmacology; Apoptosis - drug effects; Biological and medical sciences; Cell Division - drug effects; Cells, Cultured; DNA Fragmentation - drug effects; Down-Regulation; Female; Fetal Blood; General aspects; Humans; Immunoblotting; In Vitro Techniques; Interleukin-2 - antagonists & inhibitors; Interleukin-2 - pharmacology; Leukocytes, Mononuclear; Medical sciences; Pharmacology. Drug treatments; Pregnancy; Prostaglandin D2 - analogs & derivatives; Prostaglandin D2 - pharmacology; Prostaglandins A - pharmacology; Protein Biosynthesis; Recombinant Proteins - antagonists & inhibitors; Recombinant Proteins - pharmacology; RNA - biosynthesis; Uridine - metabolism; Antineoplastic agent; Human; Cell proliferation; Mononuclear cell; Interleukin 2; Cytokine; Antiviral; Mechanism of action; In vitro; Prostaglandin A1
• ISSN: 0192-0561; 1879-3495
• DOI: 10.1016/S0192-0561(96)00072-0

Cyclopentenone prostaglandins PGA1 and PGJ2 induce growth arrest at the G1/S interphase of the cell cycle in tumour cell lines. Notably, PGE, the precursor molecule of PGA, downregulates the interleukin (IL)-2-dependent proliferation of lymphocytes. Therefore the IL-2/IL-2 receptor system and relative signal transduction is a possible target of the antiproliferative effect of PGA/PGJ. In the present study the PGA1/PGJ2-dependent growth inhibition of IL-2-stimulated primary human cord blood mononuclear cells (CBMCs) was found to be mediated by interference with the IL-2 proliferative signal. Both prostaglandins (PGs) inhibited the synthesis of total RNA and protein in IL-2 stimulated cells. PGA1 and even more PGJ2 downregulated the expression of IL-2 receptor alpha (CD25 phenotype). IL-2 partly reversed this effect. Moreover, suppression of IL-2-stimulated cells was not the result of PG-mediated activation of apoptosis. On the contrary, PGs reduced both apoptosis and the high expression of c-Jun detectable in CBMCs spontaneously. Cyclin A/Cdk2 complexes regulate G1/S transition during the cell cycle. In IL-2-stimulated cells, the levels of Cdk2 were found to be lower in PG-treated cells than those detected in controls. In conclusion, cyclopentenone PGs inhibit CBMCs spontaneous or IL-2-dependent proliferation in part by interfering with the IL-2 pathway.