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  • 1. Boij, R.
    et al.
    Berg, G.
    Ernerudh, J.
    Nilsson-Ekdahl, Kristina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Svensson, J.
    Sandholm, K.
    Lindahl, T.
    Matthiesen, L.
    Jenmalm, M.
    Palonek, E.
    Jarle, M.
    Biomarkers of coagulation, inflammation and angiogenesis are independently associated with preeclampsia2012In: Journal of Reproductive Immunology, ISSN 0165-0378, E-ISSN 1872-7603, Vol. 94, no 1, p. 109-109Article in journal (Other academic)
  • 2.
    Dubicke, Aurelija
    et al.
    Department of Woman and Child Health, Karolinska Institute,Stockholm, Sweden.
    Andersson, Peter
    Stockholms universitet, Avdelningen för immunologi.
    Fransson, Emma
    Department of Woman and Child Health, Karolinska Institute, Stockholm, Sweden.
    Andersson, Eva
    Department of Woman and Child Health, Karolinska Institute,Stockholm, Sweden.
    Sioutas, Angelos
    Malmström, Anders
    Department of Experimental Medical Science, University of Lund, Sweden.
    Sverremark-Ekström, Eva
    Stockholms universitet, Avdelningen för immunologi.
    Ekman-Ordeberg, Gunvor
    Department of Woman and Child Health, Karolinska Institute, Stockholm, Sweden.
    High-mobility group box protein 1 and its signalling receptors in human preterm and term cervix2010In: Journal of Reproductive Immunology, ISSN 0165-0378, E-ISSN 1872-7603, Vol. 84, no 1, p. 86-94Article in journal (Refereed)
    Abstract [en]

    The objective of this study was to identify possible changes in mRNA and protein expression of high-mobility group box protein 1 (HMGB1) and its suggested receptors - receptor for advanced glycation end-products (RAGE) and Toll-like receptor 2 (TLR2) and TLR4 - in human cervix during pregnancy, term and preterm labor. Cervical biopsies were taken from 58 women: 20 at preterm labor, 24 at term labor, 10 at term not in labor and 4 from non-pregnant women. Real-time RT-PCR was used to quantify mRNA expression, and immunohistochemistry and ELISA for protein analysis. HMGB1, RAGE, TLR2 and TLR4 proteins were localized and their mRNA expression was detected in the cervix. There was more extranuclear HMGB1 in the cervical epithelium and stroma in preterm and term labor compared to the term not in labor. TLR2 mRNA expression was upregulated 5-fold in term labor and 3-fold in preterm labor compared to term not in labor and non-pregnant controls. There was lower expression of TLR2 and TLR4 mRNAs in preterm labor compared to term. Lower mRNA expression of HMGB1 was found in the subgroup with preterm premature rupture of membranes than in the rest of the preterm group, where levels were significantly higher than in term labor. In conclusion, extranuclear expression of HMGB1 during labor suggests a possible role of HMGB1 during the process of cervical ripening. Changes in expression of mRNAs encoding HMGB1, TLR2 and TLR4 in preterm labor suggest differences in the mechanism of cervical ripening at preterm and term delivery.

  • 3.
    Dubicke, Aurelija
    et al.
    Department of Woman and Child Health, Karolinska Institute. Stockholm, Sweden.
    Sverremark-Ekström, Eva
    Stockholms universitet.
    Fransson, Emma
    Department of Woman and Child Health, Karolinska Institutet, Stockholm, Sweden.
    Centini, Gabriela
    Department of Pediatrics, Obstetrics and Reproductive Medicine, University of Siena, 53100 Siena, Ital.
    Andersson, Eva
    Department of Woman and Child Health, Karolinska Institute. Stockholm, Sweden.
    Byström, Birgitta
    Department of Woman and Child Health, Karolinska Institute. Stockholm, Sweden.
    Ekman-Ordeberga, Gunvor
    Department of Woman and Child Health, Karolinska Institute, Stockholm, Sweden.
    Malmström, Anders Malmström
    Department of Experimental Medical Science, University of Lund, 221 84 Lund, Sweden.
    Petraglia, Felice
    Department of Pediatrics, Obstetrics and Reproductive Medicine, University of Siena, 53100 Siena, Italy.
    Pro-inflammatory and anti-inflammatory cytokines in human preterm and term cervical ripening2010In: Journal of Reproductive Immunology, ISSN 0165-0378, E-ISSN 1872-7603, Vol. 84, no 2, p. 176-185Article in journal (Refereed)
    Abstract [en]

    Cervical ripening is necessary for successful delivery. Since cytokines are believed to be involved in this process, the aim of this study was to investigate possible changes in the mRNA and protein expression of pro-inflammatory cytokines (interleukin (IL)-1 alpha, IL-1 beta, IL-12, IL-18) and anti-inflammatory cytokines (IL-4, IL-10, IL-13)in the human cervix during pregnancy, term and preterm labor. Cervical biopsies were taken from 59 women: 21 at preterm labor, 24 at term labor, 10 at term not in labor and 4 from non-pregnant women. mRNA was analyzed with real-time RT-PCR and protein expression and/or secretion with immunohistochemistry and ELISA. There was an upregulation of mRNA for IL-10, IL-13, IL-1 alpha and IL-1 beta in the laboring groups, while mRNA for IL-12 and IL-18 was downregulated. IL-4 mRNA was detected more frequently, while IL-12 mRNA expression was lower, in the preterm labor group than in the term labor group. The protein levels of IL-4 and IL-12 were lower and IL-18 tended to be higher in the labor groups, while IL-10 protein levels were unaffected by labor. IL-4 protein levels were significantly higher in the preterm subgroup with bacterial infection than in the non-infected group. IL-10 had higher expression in squamous epithelium at preterm labor than at term. In conclusion, the major changes in pro-inflammatory and anti-inflammatory cytokine mRNA and protein expression in cervix occur during the labor process irrespective of the length of gestation. Our results indicate that dysregulation of anti-inflammatory cytokines in the human cervix could be involved in the pathogenesis of preterm labor.

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