Localization of Nuclear Factor-κB (NFκB) and Inhibitory Factor-κB (IκB) in Human Fetal Membranes and Decidua at Term and Preterm Delivery

Abstract

The human fetal membranes and decidua are thought to be involved in the onset of human parturition. These tissues produce and respond to various cytokines, which may be involved in preterm labour and possibly term labour. They also show increasing production of prostaglandins (PGs) with advancing gestation and labour. The expression of PGHS-2, a rate limiting enzyme in PG synthesis, is increased in the fetal membranes at labour. The gene for PGHS-2 and many of the cytokine genes (e.g. TNFα, IL-1, IL-6) are stimulated by the transcription factor NFκB. This factor is composed of two subunits, p50 and p65, which are localized in the cytoplasm bound to IκB. When activated IκB is metabolized, and p50, p65 translocate to the nucleus to activate various genes. The purpose of the present study was to examine the tissue and cellular distribution of p65 and IκB in the human fetal membranes and decidua throughout gestation. Term tissues were obtained prior to labour by elective caesarean section (n=10) or following vaginal delivery (n=10) and 10 preterm tissues were obtained following labour prior to 37 weeks gestation. None of the tissues had any evidence of infection. The immunoreactive NFκB and IκB were localized in the tissues. p65 protein was found in the nucleus and cytoplasm of cells in the amnion, chorion laeve and decidua. In the amnion and chorion laeve, no changes occurred in subcellular localization with advancing gestation or term labour. However, in the decidua, there was a marked increase in the nuclear localization of i.r. p 65 in tissues obtained at term when compared with tissues delivered preterm. In the case of IκB, it was localized to the cytoplasm of cells in all tissues and there was an increase i.r. IκB in decidua at term compared to preterm but no change occurred in the amnion or chorion. The increase in nuclear localization of p65 in the decidua that occurs with advancing gestation, highlights the potential importance of this factor in the regulation of parturition related genes in this tissue.