A novel role for GSK3 in the regulation of the processes of XXXX labour.

@entity1 @entity32 @entity3152 @entity1356 @entity310 @entity61508 @entity20040 @entity600 @entity2938 @entity3009 @entity36459 @entity9459 @entity1495 @entity563 @entity2939 @entity2247 @entity204 @entity35466
@entity600 remains the largest single cause of @entity204 and morbidity. Infection and/or @entity32 are strongly associated with @entity3152 . Glycogen synthase kinase 3 (GSK3) is known to be a crucial mediator of @entity32 homeostasis. The aims of this study were to determine the effect of spontaneous @entity1 labour in foetal membranes and myometrium on @entity35466 /b expression, and the effect of inhibition of @entity35466 /b on pro-labour mediators in foetal membranes and myometrium stimulated with Toll-like receptor (TLR) ligands and pro-inflammatory cytokines. Term and @entity3152 in foetal membranes was associated with significantly decreased @entity563 phosphorylated @entity35466 and b expression, and thus increased GSK3 activity. There was no effect of term labour on @entity563 phosphorylated @entity9459 expression in myometrium. The specific @entity35466 /b inhibitor @entity61508 significantly decreased lipopolysaccharide (ligand to @entity2939 )-stimulated pro-inflammatory cytokine gene expression and release; @entity2247 gene expression and prostaglandin release; and @entity1495 gene expression and pro @entity1495 release in foetal membranes and/or myometrium. @entity61508 also decreased @entity36459 ( @entity2938 ligand) and flagellin ( @entity20040 ligand)-induced pro-inflammatory cytokine gene expression and release and @entity2247 mRNA expression and prostaglandin release. @entity9459 siRNA knockdown in primary myometrial cells was associated with a significant decrease in @entity1356 and @entity310 -induced pro-inflammatory cytokine and @entity3009 release. In conclusion, @entity35466 /b activity is increased in foetal membranes after term and @entity3152 . Pharmacological blockade of the kinase GSK3 markedly reduced pro-inflammatory and pro-labour mediators in @entity1 foetal membranes and myometrium, providing a possible therapeutics for the management of @entity3152 .
