
TY  - JOUR
A1  - McCracken, S. A. 
A1  - Gallery, E. D.M. 
A1  - Morris, J. M. 
T1  - 286. Nuclear factor &#954;B downregulation in human T-cells is essential for the maintenance of the cytokine profile required for pregnancy success
JF  - Reproduction, Fertility and Development
JO  - Reprod. Fertil. Dev.
Y1  - 2004
VL  - 16
IS  - 9
SP  - 286
EP  - 286
KW  - 
UR  - https://doi.org/10.1071/SRB04ABS286 
N2  - Human pregnancy is associated with a shift away from Th-1 type and a bias towards Th-2 type immune responses. The molecular mechanisms that regulate this are unknown. We assessed the expression and activity of Nuclear Factor (NF)-&#954;B, a transcription factor that plays a central role in regulating immune responses. Nuclear and cytoplasmic fractions were prepared from isolated T-cells from non-pregnant and pregnant females and subjected to Western blotting to assess NF-&#954;B and its&#39; inhibitors I&#954;B&#945; and &#946; expression. NF-&#954;B activity in nuclear extracts was determined by Electrophoretic Mobility Shift Assays. Isolated T-cells were pre-incubated with/without the NF-&#954;B translocation inhibitor SN50 and subsequently stimulated with PMA/ionomycin in the presence of the protein transport inhibitor Brefeldin A. Cytokine production was determined using flow cytometry. Our results demonstrated high levels of immunoreactive NF-&#954;B (p65) in all nuclear fractions of T-cells from non-pregnant females. In contrast, low levels of p65 were detected in nuclear fractions of T-cells from pregnant females. Levels of I&#954;B&#945; and &#946; were also higher in cytoplasmic fractions of T-cells from non-pregnant than from pregnant females. The reduction in p65 levels in pregnancy was consistent with reduced levels of active NF-&#954;B in T-cells from pregnant relative to non-pregnant females. Stimulation of T-cells from non-pregnant females with PMA/ionomycin resulted in I&#954;B&#945; degradation, p65 translocation and subsequent production of Th-1 cytokines IFN-&#946; and IL-2. In contrast, PMA stimulation had no effect on NF-&#954;B activity in T-cells from pregnant females and a reduced effect on IFN-&#946; and IL-2 production. In the presence of SN50, IFN-&#946; and IL-2 production by T-cells from non-pregnant females was attenuated demonstrating a specific role for NF-&#954;B in the production of these Th-1 cytokines. We can therefore conclude that, specific down-regulation of NF-&#954;B in T-cells in pregnancy is an essential requirement for maintaining the cytokine profile necessary for pregnancy success. 
ER  -

