Autocrine/paracrine regulation of apoptosis in epithelial cells by prostaglandin E 2

• Published in: Prostaglandins, leukotrienes and essential fatty acids Vol. 67; no. 5; pp. 357 - 363
• Main Authors: Jabbour, H.N., Kelly, R.W., Boddy, S.C.
• Format: Journal Article
• Language: English
• Published: Elsevier Ltd 01-11-2002
• ISSN: 0952-3278; 1532-2823
• DOI: 10.1054/plef.2002.0442

This study was designed to investigate the effect of IL-1α-induced up-regulation of cyclooxygenase-2 (COX-2) on prostaglandin E
2 (PGE
2) secretion and the subsequent phenotypic effects of PGE
2 on epithelial cells. The effect of IL-1α on COX-2 expression was investigated in the T24 bladder epithelial cell line following treatment with 0, 0.05, 0.5, 1 or 10 ng/ml IL-1α for 1, 2, 4 or 6 h. Quantitative PCR confirmed up-regulation of expression of COX-2 with maximal expression observed following treatment with 0.5 ng/ml IL-1α for 1 h. Co-treatment of the cells with 0.5 ng/ml IL-1α in the presence or absence of 100 ng/ml IL-1 receptor antagonist (RA) abolished the up-regulation in COX-2 expression confirming that the effect of IL-1α is mediated via its membrane-bound receptors. Treatment with 0.5 ng/ml IL-1α resulted in a time-dependent increase in PGE
2 secretion with maximal secretion detected at 24 and 48 h after stimulation with IL-1α. Co-treatment of the cells with IL-1α and IL-1RA or the COX-2 enzyme inhibitor NS398 abolished the IL-1α mediated secretion of PGE
2. Treatment of T24 cells with 100 nM PGE
2 resulted in a significant elevation in cAMP generation confirming the expression of functional PGE
2 receptors. Finally, the effect of exogenous treatment with PGE
2 on apoptosis of T24 cells was assessed using cell death detection ELISA. T24 cells were treated with camptothecin to induce apoptosis in the presence or absence of 50 or 100 nM PGE
2 or 10 μM forskolin. Treatment of T24 cells with increasing doses of camptothecin alone resulted in a significant increase in the induction of apoptosis (
P<0.01). However, co-treatment of the cells with 50 or 100 nM PGE
2 or 10 μM forskolin resulted in the inhibition of induction of the apoptotic pathway by camptothecin. These data demonstrate that PGE
2 inhibits apoptosis of epithelial cells possibly via cAMP-dependent pathway.