Cnr2 Deficiency Confers Resistance to Inflammation-Induced Preterm Birth in Mice

Infection-induced inflammation, frequently associated with increased production of proinflammatory cytokines, is considered a significant contributor to preterm birth. A G protein-coupled cannabinoid receptor 2 (CB2), encoded by Cnr2, is expressed in various immune cells and was shown to modulate im...

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Bibliographic Details
Published in:Endocrinology (Philadelphia) 2014-10, Vol.155 (10), p.4006-4014
Main Authors: Sun, Xiaofei, Cappelletti, Monica, Li, Yingju, Karp, Christopher L, Divanovic, Senad, Dey, Sudhansu K
Format: Article
Language:English
Subjects:
Accumulation
Animals
Birth
Cannabinoid CB2 receptors
Cyclic AMP
Cytokines - blood
Dendritic cells
Female
Immune system
Inflammation
Inflammation - blood
Inflammation - chemically induced
Inflammation - complications
Inflammation - genetics
Interleukin 10
Interleukin 6
Lipopolysaccharides
Male
Mice
Mice, Inbred C57BL
Mice, Knockout
Pregnancy
Premature birth
Premature Birth - blood
Premature Birth - etiology
Premature Birth - genetics
Progesterone
Progesterone - blood
Receptor, Cannabinoid, CB2 - genetics
Reproduction-Development
Serum levels
Toll-Like Receptor 4 - genetics
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Summary:Infection-induced inflammation, frequently associated with increased production of proinflammatory cytokines, is considered a significant contributor to preterm birth. A G protein-coupled cannabinoid receptor 2 (CB2), encoded by Cnr2, is expressed in various immune cells and was shown to modulate immune responses. We show here that Cnr2, but not Cnr1, deficient mice are resistant to lipopolysaccharide (LPS)-driven preterm birth and suppression of serum progesterone levels. After LPS challenge, Cnr2−/− mice exhibited increased serum levels of IL-10 with decreased IL-6 levels. These changes were associated with reduced LPS-induced Ptgs2 expression at the maternal-conceptus interface on day 16 of pregnancy. LPS stimulation of Cnr2−/− dendritic cells in vitro resulted in increased IL-10 with reduced IL-6 production and correlated with increased cAMP accumulation. Collectively, our results suggest that increased IL-10 production occurring via augmented cAMP accumulation represents a potential mechanism for the resistance of Cnr2−/− mice to LPS-induced preterm birth. These results may have clinical relevance, because currently, there are limited options to prevent preterm birth.
ISSN:0013-7227
1945-7170
DOI:10.1210/en.2014-1387