title: 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 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.
authors: Division of Reproductive Sciences (X.S., Y.L., S.K.D.), Perinatal Institute, and Division of Cellular and Molecular Immunology (M.C., C.L.K., S.D.), Cincinnati Children's Research Foundation, Cincinnati, Ohio 45229.
authors: Xiaofei
authors: X
authors: Sun
authors: Monica
authors: M
authors: Cappelletti
authors: Yingju
authors: Y
authors: Li
authors: Christopher L
authors: CL
authors: Karp
authors: Senad
authors: S
authors: Divanovic
authors: Sudhansu K
authors: SK
authors: Dey
mesh_terms: D000818:Animals; D016207:Cytokines / Q000097:blood; D005260:Female; D007249:Inflammation / Q000097:blood / Q000139:chemically induced / Q000150:complications* / Q000235:genetics; D008070:Lipopolysaccharides; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011247:Pregnancy; D047928:Premature Birth / Q000097:blood / Q000209:etiology* / Q000235:genetics; D011374:Progesterone / Q000097:blood; D043885:Receptor, Cannabinoid, CB2 / Q000235:genetics*; D051197:Toll-Like Receptor 4 / Q000235:genetics
chemical_list: C571431:Cnr2 protein, mouse; D016207:Cytokines; D008070:Lipopolysaccharides; D043885:Receptor, Cannabinoid, CB2; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4; D011374:Progesterone