engleski

Expression of HSP90 family members and their receptors at maternal fetal interface of early healthy human pregnancy

INTRODUCTION: Members of heat shock protein (HSP) 90 family consists of HSP90 and gp96. They are highly conserved molecules. HSP maintain cell homeostasis. Released in the extracellular space, from necrotic cells or by active cellular secretion, HSPs by themselves and in the complex with peptides become forceful immunogens. Extracellular HSP acts through binding to surface receptors on antigen presenting cells, stimulating proinflammatory response, which might be harmful in pregnancy and may lead to the maternal immune rejection directed toward fetus. The aim of our study was to investigate the expression and distribution of gp96 and HSP90, as well as their receptors CD91 and TLR4 at the maternal fetal interface. Particular attention was driven to regulation of their receptors with progesterone's mediator progesterone inducing blocking factor (PIBF) in vitro. MATERIAL AND METHODS: Immunohistology was used to detect presence and localization of gp96, HSP90, CD91 and TLR4 in paraffin embedded normal early pregnancy decidual tissue sections. The distribution and frequency of CD91 and TLR4 was investigated in decidual mononuclear cell suspensions, obtained by enzymatic digestion and gradient density centrifugation, by multicolor immunofluorescence and flow cytometry. CD91 mRNA was detected by quantitative RT-PCR using Taqman probes (AB 7300 Real -Time PCR system). RESULTS: Abundant gp96 and HSP90 positive cells were found in the decidual glandular epithel and trophoblast cells at the maternal fetal interface of early pregnanc. There are also present the receptors for HSP, CD91 and TLR4. PIBF statisticly significantly decreased precentage of TLR4 positive T cells and the frequency of CD91 expressing NK and CD83+ cells in isolated suspension of decidual mononuclear cells. Quantitative RT-PCR results indicate that CD91 mRNA is down-regulate by PIBF in decidual mononuclear cell suspensions. CONCLUSION: The presence of gp96, HSP90 and their cognate receptors CD91 and TLR4 at the maternal fetal interface implies molecular basis for their tissue specific interaction regulated by thespecific progesterone's action.

CD 91; decidua; glycoprotein 96; HSP 90; progesterone induced blocking factor; toll like receptor 4; pregnancy

nije evidentirano