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Regulation of glycoprotein 96 and CD91 with specific action of progesterone, interleukin 2 and interleukin 15 in the first trimester decidual leucocytes

Heat shock proteins (hsps) by themselves or in the complex with peptides, whose structure protected intracellular, become forceful antigens if released, after the binding with CD91 receptor on immune cells. This interaction might bias the immune response towards the Th1 pattern and could cause undesirable pregnancy termination. We investigated the expression of gp96 and CD91 receptor in the first trimester normal human pregnancy decidua and term pregnancy, as well as the regulation of gp96 and CD91 in isolated early decidual mononuclear cells (DMCs) after Progesterone inducing blocking factor (PIBF), interleukin (IL)-15 or IL-2 stimulation in vitro. MATERIAL AND METHODS: DMCs were isolated from early human decidua by collagenase IV digestion and gradient density centrifugation and stimulated overnight with PIBF, IL-15 or IL-2. The expression of CD91and gp96 were analysed by flow cytometry (FACSCalibur, BD) and Applied Biosystems 7300 Real-Time PCR System. The immunohistology and immunofluorescence were applied to detect gp96, CD91 and/or cytokeratin in paraffin embedded tissue sections of early human pregnancy decidua and term placenta. The data were analysed using the Alphelys Spot Browser 2 integrated system. RESULTS: The number and staining intensity of gp96 and CD91 did not differ between the first trimester pregnancy decidua and term placenta. Glandular and trophoblast cells were positive for both antigens. CD83+ cells show the highest frequency of CD91+ cells among isolated early DMCs. PIBF decreased CD91 protein expression on the surface of CD83+ and T cells, and mRNA for CD91 and gp96 in DMCs on a dose dependent manner, when compared to control. IL-2 diminished frequency of CD91 expressing CD1a+ and CD83+ dendritic cells, whereas IL-15 increased the frequency of CD91+ cells within rare CD56+bright NK subset and entire NK subpolulation in vitro. Both, IL-2 and IL-15 diminished CD91 mRNA, however increased gp96 mRNA in DMCs on a dose dependent manner. CONCLUSION: Gp96/CD91 expression at the implantation site could be influenced by the interplay among PIBF, IL-15 and IL-2.

CD91; fetaloplacental unit; glycoprotein 96; Progesterone Induced Blocking Factor; pregnancy; IL-2; IL-15

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