A role for IL-17 in induction of an inflammation at the fetomaternal interface in preterm labour.

Department of Obstetrics and Gynecology, University of Toyama, Toyama-shi, Toyama, Japan.
Journal of Reproductive Immunology (Impact Factor: 2.37). 12/2009; 84(1):75-85. DOI: 10.1016/j.jri.2009.09.005
Source: PubMed

ABSTRACT Chorioamnionitis (CAM) is a major cause of preterm delivery. Inflammatory cytokines and chemokines play important roles in the pathogenesis of preterm delivery. Interleukin (IL)-17 is a key cytokine which induces inflammation and is critical to host defense. In this study, we examined the role of IL-17 in the pathogenesis of preterm delivery. The levels of cytokines including IL-17, IL-8 and tumor necrosis factor (TNF) alpha were measured by ELISA in amniotic fluid from 154 cases of preterm labor. Flow cytometry and immunohistochemical staining were performed to determine the distribution of IL-17-producing cells. IL-8 secretion was evaluated in primary cultured human amniotic mesenchymal (HAM) cells and human amniotic epithelial (HAE) cells stimulated with IL-17, TNFalpha or IL-1beta. We also studied the signaling pathway of IL-17 and TNFalpha in HAM cells. Levels of inflammatory cytokines in amniotic fluid were higher in preterm delivery cases than in term delivery cases. Furthermore, IL-8, IL-17 and TNFalpha levels were significantly higher in the preterm cases with CAM stage II or III than those without CAM. Flow cytometry and immunohistochemical staining revealed that CD3(+)CD4(+) T cells were the main source of IL-17 in the chorioamniotic membrane. Interestingly, TNFalpha-induced IL-8 secretion was enhanced by IL-17 in a dose-dependent manner in HAM cells. The IKK inhibitor BMS-345541 and mitogen-activated protein kinase (MAPK) inhibitors p38, JNK and p42/44 (ERK1/2 pathway) reduced IL-8 secretion by IL-17-stimulated and TNFalpha-stimulated HAM cells. These results indicate that IL-17, produced by T cells, promotes inflammation at the fetomaternal interface in preterm delivery.

Download full-text


Available from: Koichi Tsuneyama, Dec 13, 2013
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The aim of this study was to estimate the prevalence of CD3(+)CD4(+) T lymphocytes producing IL-17, IL-2, IFN-γ, and IL-4, plus CD4(+)CD25(+)FoxP3(+) T regulatory (Treg) cells, in peripheral blood of patients with preeclampsia and healthy women in the third trimester of normal pregnancy. Another purpose was to assess the immunosuppressive activity of Treg cells from patients with preeclampsia compared with controls. Thirty-four preeclampsia patients and 27 healthy pregnant women were included. The percentages of CD4(+)CD25(+)FoxP3(+) Treg cells and CD3(+)CD4(+) T lymphocytes with intracellular expressions of cytokines were estimated using monoclonal antibodies and flow cytometry. In vitro functional assays were performed using a Treg Cell Isolation Kit and (3)H-thymidine incorporation assays. The percentage of CD3(+)CD4(+) T lymphocytes producing IL-17A was significantly higher in preeclampsia than in healthy, normotensive pregnant women in the third trimester (p<0.001). The population of CD4(+)CD25(+)FoxP3(+) Treg cells was significantly lower in the study group compared with controls (p<0.05). There was no change in the stimulation index of CD3(+)CD4(+)CD25(-) T lymphocytes from preeclampsia patients without Treg cells and after addition of autologous Treg cells. In normal pregnancy, the stimulation index of CD3(+)CD4(+)CD25(-) T lymphocytes was significantly higher without Treg cells compared with the response after addition of autologous Treg cells (p<0.05). The results suggest up-regulation of the Th17 immune response in preeclampsia. The decreased number and function of Treg cells may be responsible for activating the inflammatory response characteristic of this disorder. In preeclampsia, the predominance of Th17 immunity could act through modulating the Th1/Th2 immune balance.
    Journal of Reproductive Immunology 02/2012; 93(2):75-81. DOI:10.1016/j.jri.2012.01.006 · 2.37 Impact Factor
  • Source
    Autoimmune Disorders - Pathogenetic Aspects, 10/2011; , ISBN: 978-953-307-643-0
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Th17 cells, a new subset of helper T cells, have been focused on as a producer pro-inflammatory cytokines. It is, however, still unknown how Th17 cells affect pregnancy outcome. We investigated the expression of IL-17-producing cells in human spontaneous abortion. IL-17 expression was analyzed in decidual tissues among normal pregnancy, missed abortion, and inevitable abortion cases by immunohistochemistry and flow cytometry. IL-17+ cells were accumulated in decidua and were detected in decidual CD4+ T cells and few decidual CD8+ T cells in spontaneous abortion cases. The number of decidual IL-17+ cells in inevitable abortion cases involving active genital bleeding was significantly higher than that in normal pregnancy cases (P < 0.05). On the other hand, there were no significant differences in the numbers of decidual IL-17+ cells between missed abortion cases and normal pregnancy subjects. Furthermore, the number of IL-17+ cells was positively correlated with the number of neutrophils in spontaneous abortion cases. IL-17+ cells might be involved in the induction of inflammation in the late stage of abortion, but not in the early stage of abortion.
    American Journal Of Reproductive Immunology 03/2010; 64(1):4-11. DOI:10.1111/j.1600-0897.2010.00812.x · 3.32 Impact Factor