The NF-kappa B pathway in human endometrium and first trimester decidua

Nuclear factor kappa B (NF-kappaB) regulates proinflammatory genes and may be involved in inflammation associated with reproductive events e,g. menstr uation, implantation. Activation of NF-kappaB involves several protein kina ses and subsequent degradation of an endogenous inhibitor, I kappaB alpha, This study details expression of NF-kappaB pathway intermediates in human e ndometrium and first trimester decidua, Messenger RNA was detected for I ka ppaB alpha, and I kappaB kinase gamma (IKK gamma, a scaffolding protein) an d the protein kinases, IKK alpha, IKK beta, NF-kappaB inducing kinase (NIK) , mitogenactivated protein kinase Erk kinase kinase 1 (MEKK1) and TANK-bind ing kinase 1 (TBK1) using real-time quantitative polymerase chain reaction (PCR), I kappaB alpha and TBK1 mRNA were increased in the perimenstrual pha se of the menstrual cycle, This suggests that there is activation of NF-kap paB due to premenstrual progesterone withdrawal, since NF-kappaB activity i ncreases I kappaB alpha gene expression. Differential expression of NF-kapp aB pathway intermediates occurred when progesterone concentrations increase d in early pregnancy; IKK alpha and NIK mRNA levels increased in decidua wh ilst IKK beta and MEKK1 mRNA levels declined. Expression profiles of IKK al pha and NIK proteins were determined immunohistochemically. Both were detec ted in glandular epithelium and endothelium of endometrium, In decidua, bot h were present in epithelium and decidualized stromal cells. The results of this study suggest that NF-kappaB is activated during menstruation. During early pregnancy, NF-kappaB may also be activated (via IKK alpha -NIK) and may regulate the expression of molecules vital for implantation and success ful pregnancy. However, proinflammatory signalling to NF-kappaB (via IKK be ta -MEKK1) may be down-regulated in early pregnancy, contributing to the im munosuppressive mechanisms which prevail at this time.