SUMMARYThe placenta constitutes a physical and immunological barrier against invading infectious agents and has been suggested to be a pregnancy-specific component of the innate immune system. The aim of this study was to investigate the presence and regulation of Tolllike receptors-2 and -4 (TLR2 and TLR4) in the human placenta, because these receptors are believed to be important for immune responses against pathogens. Twenty-eight placentas from normal term pregnancies were analysed with immunohistochemistry, which showed a strong immunoreactivity for TLR2 and TLR4 in the villous and the intermediate trophoblasts. The regulation of TLR2 and TLR4 by microbial stimulus was assessed by incubating explants of term chorionic villi with zymosan or lipopolysaccharide (LPS) and analysed with real-time reverse transcriptase-polymerase chain reaction. Stimulation with zymosan and LPS readily induced interleukin (IL)-6 and IL-8 cytokine production in the placenta cultures, whereas TLR2 and TLR4 mRNA and protein expression remained at the same high level as in unstimulated explants. These data suggests a novel mechanism for the fetoplacental unit to interact with micro-organisms.

The novel inflammatory cytokine high mobility group box protein 1 (HMGB1) is expressed by human term placenta IntroductionPregnancy is an immunological challenge in which the mother carries the fetus-essentially a non-self invader-for an extended period of time. The barrier between the two entities is the placenta. The fetal part of the placenta consists of the two membranes, amnion and chorion, the umbilical cord and the chorionic villi covered by the syncytiotrophoblast, while the decidua and the intervillous space belong to the maternal part of the placenta. 1 The process of human labour involves contractionassociated proteins, inflammatory cytokines, prostaglandins and extracellular matrix remodelling. 2 Furthermore, the nuclear factor-jB (NF-jB) family is an upstream regulator of multiple labour-associated processes. An increase in gene expression of multiple cytokines and chemokines known to be involved in acute inflammation has been observed in chorioamniotic membranes from patients in labour compared to membranes from those not in labour. 3 Pre-eclampsia is a pregnancy-related disorder that affects women all over the world and is a major cause of maternal and fetal morbidity and mortality. Major maternal symptoms include hypertension, abnormal amounts SummaryHigh mobility group box protein 1 (HMGB1) was previously considered a strict nuclear protein, but lately data are accumulating on its extranuclear functions. In addition to its potent proinflammatory capacities, HMGB1 has a prominent role in a number of processes of specific interest for the placenta. Our overall aim was to investigate the expression of HMGB1 in human term placenta and elucidate a potential difference in HMGB1 expression comparing vaginal deliveries with elective Caesarean sections. In addition, placentas from normal pregnancies were compared with placentas from pregnancies complicated by pre-eclampsia. Twenty-five placentas, 12 from normal term pregnancies and 13 from pregnancies complicated by pre-eclampsia were analysed with immunohistochemistry for HMGB1 and its putative receptors; receptor for advanced glycation end-products (RAGE), Toll-like receptor 2 (TLR2) and TLR4. We present the novel finding that in addition to a strong nuclear HMGB1 expression in almost all cells in investigated placentas, an individual variation of cytoplasmic HMGB1 expression was detected in the syncytiotrophoblast covering the peripheral chorionic villi, by cells in the decidua and in amnion. Production of HMGB1 was confirmed by in situ hybridization. Although labour can be described as a controlled inflammatory-like process no differences in HMGB1 expression could be observed comparing active labour and elective Caesarean sections. However, a tendency towards a higher expression of cytoplasmic HMGB1 in the decidua from women with pre-eclampsia was demonstrated. The abundant expression of the receptors RAGE, TLR2 and TLR4 implicates a local capability to respond to HMGB1, although the precise role in the placenta remains to be elucidated. of protei...

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SummaryBreast milk contains pro-and anti-inflammatory cytokines and chemokines with potential to influence immunological maturation in the child. We have shown previously that country of birth is associated with the cytokine/ chemokine profile of breast milk. In this study we have investigated how these differences in breast milk affect the cellular response of cord blood mononuclear cells (