Cnr2 deficiency confers resistance to inflammation- induced preterm birth in mice

Abstract

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 variousimmunecells and wasshown to modulate immune responses.Weshow 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 maternalconceptus 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. Copyright