ИСТИНА

Progesterone (P4) ensures pregnancy preservation and prevents allogeneic fetal rejection. The mechanism of P4 action on immune cells is not well understood. The effects of progestins are mediated both by nuclear (nPRs) and membrane receptors (mPRs) of the progestin and adipoQ receptor family. The mPRα and mPRβ are expressed in T lymphocytes, whereas the nPRs expression is not detected. Among the synthesized compounds, we identified two selective ligands of mPRs that do not interact with nPRs: 19-hydroxypregn-4-en-20-one (I) and 19-hydroxypregn-3-en-20-one (II). We assessed the effects of these compounds and P4 on the levels of cytokines (IL-2, IL-10, TGF beta and TNF alpha) mRNA in Jurkat cells by means of qRT-PCR. Cells were stimulated with phorbol esters and incubated with hormones (1 to 50 μM) for 48 hours. Such concentrations can be detected locally, near the sites of P4 synthesis during pregnancy. 1-10 μM of any steroid did not significantly influence the cytokines mRNAs levels. A 20 μM P4 and both selective ligands significantly reduced the TNF-alpha mRNA level (by about 30% compared to the control), a 50 μM P4 reduced it even more, whereas I and II little changed their effects. The IL-2 mRNA level declined significantly after exposure to P4 and compound I at both concentrations, but not after the treatment with II. The IL-10 mRNA level significantly increased under the action of 50 μM P4 and compound II. None of the three steroids caused changes in the TGF-beta mRNA level. Therefore, progestins suppress the levels of pro-inflammatory TNF-alpha and IL-2 mRNA and augment the IL-10 mRNA level through mPRs in T-cells. The differences in effects of compounds I and II may be due to their different affinity for the mPR α and β subtypes, whereas P4 binds to both mPRs.