engleski

The role of progesterone in regulation of perforin expression in decidual and peripheral blood lymphocytes

Human first trimester pregnancy decidua is characterised by high local concentration of progesterone and infiltration of bone marrow derived cells (decidual leukocytes), which are in situ surrounded with decidual stromal cells and macrophages. It is known that all these cells are rich source of cytokines with autocrine and paracrine actions. Decidual nonadherent cells (NAC) are prevalently (85-90%) non-classical NK cells with CD16- CD56bright+ phenotype and high level of perforin (P) and serine esterases in their granules. Both, content of P per cell and the percent of P positive cells diminish after 18h incubation in vitro, but it can be prevented completely by cocultivation with adherent cells. The presence of macrophages in the suspension of adherent cells (AC) is essential for this effect. We investigated whether progesterone directly by itself, or indirectly by some mediators (PIBF - Progesterone Induced Blocking Factor) can modulate P expression in decidual and peripheral blood NAC cultivated either alone, or with decidual/peripheral blood AC. Progesterone in lower concentrations did not affect perforin expression, but when added in high concentration (20 g/ml) strong downregulation was obtained, as well as a blockade of upregulation in decidual NAC, but not peripheral blood NAC, cocultivated with decidual AC and their supernatants. PIBF as a mediator of progesterone effects on immune functions prevents upregulation of P expression by adherent cells in the suspension of decidual NAC, but not in the suspension of peripheral blood NAC. These results point that progesterone, present in high concentrations locally at the materno-fetal interface, and in the background of cytokine network is crucial for regulation of P expression and cytolytic pathways function in decidua, but does not have so profound effects in the peripheral blood of pregnant women.

perforin; pregnancy; progesterone; PIBF; dLGL

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