PGE2 confers survivin-dependent apoptosis resistance in human monocyte-derived dendritic cells
Open Access
- 20 May 2005
- journal article
- Published by Oxford University Press (OUP) in Journal of Leukocyte Biology
- Vol. 78 (2), 555-564
- https://doi.org/10.1189/jlb.1004569
Abstract
Control of apoptosis is fundamental for dendritic cell (DC) homeostasis. Numerous factors maintain DC viability throughout their lifespan, including inhibitor of apoptosis proteins. Among them, survivin is overexpressed in many human malignancies, but its physiological function in normal cells has not been fully delineated. Prostaglandin E2 (PGE2), also overproduced in several malignancies, has shown to induce proapoptotic and antiapoptotic effects in different cell types, including immune cells. In DC, PGE2 predominantly affects maturation and modulates immune functions. Here, we show that exposure of monocyte‐derived DC to PGE2 (10−5 M) for 72 h significantly increased DC survivin mRNA and protein expression. In contrast, DC, matured with lipopolysaccharide or tumor necrosis factor α, did not reveal survivin induction in response to PGE2. Following exposure to apoptotic stimuli, DC treated with PGE2 exhibited an overall increased viability compared with control DC, and this effect was correlated inversely with caspase‐3 activation. Moreover, PGE2‐treated, survivin‐deficient DC demonstrated reduced viability in response to apoptotic stimuli. Further analysis indicated that PGE2 induced DC survivin expression in an E prostanoid (EP)2/EP4 receptor and phosphatidylinositol‐3 kinase‐dependent manner. These findings suggest that PGE2‐dependent regulation of survivin is important in modulating apoptosis resistance in human DC.Keywords
Funding Information
- UCLA Lung Cancer (SPORE P50 CA 90388, R01 CA85686)
- Medical Research Funds from the Department of Veteran Affairs
- Research Enhancement Award Program in Cancer Gene Medicine
- Tobacco-Related Disease Research Program of the University of California
- NIH (CA-16042, AI-28697)
- Jonsson Cancer Center
- UCLA AIDS Institute
- UCLA Geffen School of Medicine
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