engleski

THE ROLE OF GP96 AND ITS RECEPTORS CD91 AND TLR4 AT MATERNAL FETAL INTERFACE OF EARLY HUMAN PREGNANCY

INTRODUCTION: Heat shock proteins (HSPs) have been identified as a critical component of very complex and highly conserved cellular defense mechanisms maintain to preserve cell survival under adverse environmental conditions. In addition, HSPs are also potent activators of the cellular immune response when released by cell death caused by trauma, infection, or necrosis. Tissue remodeling at maternal fetal interface is associated with necrosis of various cell types that are potential source of extracellular HSP. Extracellular HSP acts through binding to surface receptors on antigen presenting cells, stimulating proinflammatory response, which may lead to reproductive failure. The aim of our study was to evaluate the expression and distribution of gp96 and its receptors CD91 and TLR4 in the first trimester of normal and pathological pregnancy decidua and term placenta. The role of Progesterone Induced Blocking Factor (PIBF) in the regulation of gp96 and its receptors was investigated in vitro. MATERIAL AND METHODS: Immunohistology was used to detect presence and localization of gp96, CD91 and TLR4 in paraffin embedded tissue sections of the first trimester pregnancy decidua and the term placenta. Gene levels of gp96, TLR4 and CD91 were detected in decidual mononuclear cells treated with PIBF by quantitative RT-PCR (AB 7300 Real -Time PCR system). RESULTS: Gp96 protein was more intensively labelled in the trophoblas and uterine decidua of pathological pregnancies contrary to normal pregnancy, although the TLR4 and CD91 protein expression was lower. Abundant gp96, CD91 and TLR4 positive cells were found in chorionic villi at term placenta. Upon to treatment with progesterone mediator PIBF the mRNA levels of CD91, TLR4 and gp96 were down regulated in dose dependent manner in decidual mononuclear cell suspensions. CONCLUSION: The increased presence of gp96 in pathological pregnancies may have important implication on molecular basis in the development of pathological process. PIBF down-regulates CD91 and TLR4 gene expression controlling that way the initiation of the immune response in normal early pregnancy decidua. Acknowledgement: The experiments were financed by Croatian Ministry of Science, Education and Sports Grants No. 062- 0620402-0376, 0620402-0377 and 620402-0379.

gp96; CD91 and TLR4; pregnancy

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