Critical paracrine interactions between TNF-alpha and IL-10 regulate lipopolysaccharide-stimulated human choriodecidual cytokine and prostaglandin E-2 production

Sato, Timothy A., Keelan, Jeffrey A. and Mitchell, Murray D. (2003) Critical paracrine interactions between TNF-alpha and IL-10 regulate lipopolysaccharide-stimulated human choriodecidual cytokine and prostaglandin E-2 production. Journal of Immunology, 170 1: 158-166.


Author Sato, Timothy A.
Keelan, Jeffrey A.
Mitchell, Murray D.
Title Critical paracrine interactions between TNF-alpha and IL-10 regulate lipopolysaccharide-stimulated human choriodecidual cytokine and prostaglandin E-2 production
Journal name Journal of Immunology   Check publisher's open access policy
ISSN 0022-1767
1550-6606
Publication date 2003-01-01
Sub-type Article (original research)
Volume 170
Issue 1
Start page 158
End page 166
Total pages 9
Place of publication Bethesda, MD U.S.A.
Publisher American Association of Immunologists
Language eng
Subject 1103 Clinical Sciences
1115 Pharmacology and Pharmaceutical Sciences
Formatted abstract
Increased production of PGs by gestational membranes is believed to be a principal initiator of term and preterm labor. Intrauterine infection is associated with an inflammatory response in the choriodecidua characterized by elevated production of cytokines and PGs. The precise physiological significance of enhanced choriodecidual cytokine production in the mechanism of preterm labor remains uncertain. These studies were undertaken to dissect the roles and regulation of endogenous cytokines in regulating PG production by human choriodecidua. We used LPS treatment of human choriodecidual explants as our model system. In choriodecidual explant cultures, LPS (5 μg/ml) induced a rapid increase in TNF-α production, peaking at 4 h. In contrast, IL-10, IL-1β, and PGE2 production rates peaked 8, 12, and 24 h, respectively, after LPS stimulation. Immunoneutralization studies indicated that TNF-α was a primary regulator of IL-1β, IL-10, and PGE2 production, while IL-1β stimulated only PGE2 production. Neutralization of endogenous IL-10 resulted in increased TNF-α and PGE2 production. IL-10 treatment markedly decreased TNF-α and IL-1β production, but had no effect on PGE2 production. Taken together, these results demonstrate that the effects of LPS on choriodecidual cytokine and PG production are modulated by both positive and negative feedback loops. In the setting of an infection of the intrauterine, TNF-α may be a potential target for treatment intervention; IL-10 could be one such therapeutic.
Keyword Tumor-necrosis-factor
Human Polymorphonuclear Leukocytes
Pro-Inflammatory Cytokines
Human Gestational Tissues
Labor-Associated Changes
Preterm Labor
Fetal Membranes
15-Hydroxyprostaglandin Dehydrogenase
Factor Receptor
Bacterial Lipopolysaccharide
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Unknown

Document type: Journal Article
Sub-type: Article (original research)
Collection: UQ Centre for Clinical Research Publications
 
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Created: Thu, 26 Aug 2010, 13:13:58 EST