Gene Expression Profiling of Human Decidual Macrophages: Evidence for Immunosuppressive Phenotype

Background: Although uterine macrophages are thought to play an important regulatory role at the maternal-fetal interface, their global gene expression profile is not known. Methodology/Principal Findings: Using micro-array comprising approximately 14,000 genes, the gene expression pattern of human first trimester decidual CD14+ monocytes/macrophages was characterized and compared with the expression profile of the corresponding cells in blood. Some of the key findings were confirmed by real time PCR or by secreted protein. A unique gene expression pattern intrinsic of first trimester decidual CD14+ cells was demonstrated. A large number of regulated genes were functionally related to immunomodulation and tissue remodelling, corroborating polarization patterns of differentiated macrophages mainly of the alternatively activated M2 phenotype. These include known M2 markers such as CCL-18, CD209, insulin-like growth factor (IGF)-1, mannose receptor c type (MRC)-1 and fibronectin-1. Further, the selective up-regulation of triggering receptor expressed on myeloid cells (TREM)-2, alpha-2-macroglobulin (A2M) and prostaglandin D2 synthase (PGDS) provides new insights into the regulatory function of decidual macrophages in pregnancy that may have implications in pregnancy complications. Conclusions/Significance: The molecular characterization of decidual macrophages presents a unique transcriptional profile replete with important components for fetal immunoprotection and provides several clues for further studies of these cells.Original Publication:Charlotte Gustafsson (Lidström), Jenny Mjösberg, Andreas Matussek, Robert Geffers, Leif Matthiesen, Göran Berg, Surendra Sharma, Jan Buer and Jan Ernerudh, Gene expression profiling of human decidual macrophages: Evidence for immunosuppressive phenotype, 2008, PLoS ONE, (3), 4, e2078.http://dx.doi.org/10.1371/journal.pone.0002078Copyright: Public Library of Science (PLoS)http://www.plos.org

Healthy diets and telomere length and attrition during a 10-year follow-up

Background Telomeres are repeats of DNA that contain the sequence TTAGGG at the ends of each chromosome, and their function is to protect DNA from damage. Little evidence exists regarding the relationship between dietary patterns and telomere length, especially derived applying longitudinal design. The aim was to study if overall dietary pattern is associated with leukocyte telomere length (LTL) or faster telomere attrition or both. Methods The setting was longitudinal and observational. Participants were 456 men and 590 women whose birth settled in between 1934 and 1944 and who participated in the Helsinki Birth Cohort Study. Baltic sea diet score (BSDS), modified Mediterranean diet score (mMED), and dietary inflammatory index (DII (R)) were calculated based on a 128-item food frequency questionnaire (FFQ) collected in 2001-2004. LTL was measured twice, in 2001-2004 and in 2011-2013 by quantitative real-time polymerase chain reaction. Association between the dietary patterns and LTL were analysed by general linear models with appropriate contrasts. Results BSDS, mMED, and DII did not associate with LTL in the cross-sectional analysis in men or women. Higher mMED at baseline (2001-2004) was associated with slightly faster LTL shortening during the follow-up (standardized beta -0.08, 95% CI -0.15, -0.01). No association between mMED and LTL change was found in men. Adherence to BSDS and DII did not associate with LTL change in men or women. Conclusion Baltic sea diet, Mediterranean diet, and diet's inflammatory potential seem to have only little impact on telomere length and telomere attrition in elderly Finnish men and women.Peer reviewe

Hepatocyte growth factor regulates human trophoblast motility and invasion: a role for nitric oxide

1. The expression of hepatocyte growth factor (HGF) is essential for normal placental development although its function is unknown. In this study we examined the effect of HGF on trophoblast cell motility and invasion of fibrin gels and investigated the possible role of nitric oxide (NO) in this process. 2. The human extravillous trophoblast cell line SGHPL-4 express both the constitutive and inducible isoforms of nitric oxide synthase (NOS). 3. HGF significantly stimulates cell motility in monolayer culture, the invasion of fibrin gels and the production of guanosine 3′:5′-cyclic monophosphate (cyclic GMP). 4. Invasion, motility and cyclic GMP production were inhibited by N(g)-monomethyl-L-arginine (L-NMMA). 5. Cell motility was also significantly inhibited by the inducible NOS specific inhibitor 1400 W. 6. Neither 8 Br-cyclic GMP nor the NO donor spermine-NO had any significant effect on basal trophoblast cell motility. 7. The data presented in this study demonstrate a direct effect of trophoblast-derived NO synthesis on trophoblast cell function and support the idea that HGF is involved in the regulation of trophoblast invasion through mechanisms that involve the production of NO. However neither exogenous NO nor activation of cyclic GMP-dependent pathways alone are sufficient to stimulate trophoblast cell motility