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: 2.82). 12/2009; 84(1):75-85. DOI: 10.1016/j.jri.2009.09.005
Source: PubMed


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.

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Available from: Koichi Tsuneyama, Dec 13, 2013
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    • "Nakashima et al. found also a high number of IL-17 positive cells in decidua of abortion case and suggested that Th17 cells could be involved in induction of inflammation in the late stage of abortion (53). Ito et al. suggested that Th17 cells could promote inflammation at the feto-maternal interface in preterm delivery, a disorder associated with infection and uterine inflammation (54). Furthermore, it was shown that circulating Th17 cells are increased in PE patients compared with healthy pregnant women (17). "
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    • "In particular, inappropriate activation of the immune system may be associated with the development of this syndrome. Preeclampsia is characterized as a state of the excessive maternal inflammatory response with a predominance of the production of Th1 cytokines, such as IL-2, IL-6, IL-8, IFN-␥, TNF-␣, as well as IL-12 (Saito et al., 1999; Darmochwal-Kolarz et al., 2002; Saito and Sakai, 2003; Sakai et al., 2004; Tosun et al., 2010; Redman and Sargent, 2007). "
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    • "The alterations of Th17 cells have been observed in other pregnancy-related disorders as well, suggesting that the balance of Th17 cells and Tregs and not only that of Th1 and Th2 cells has crucial effects on the inflammatory status in human pregnancy. Ito et al. recently demonstrated the importance of IL-17-producing cells in the pathomechanism of preterm labour (Ito et al., 2010). Nakashima et al. found that the prevalence of decidual IL-17- producing cells is significantly higher in inevitable abortion cases (but not in missed abortion) than in normal pregnancy, indicating that these cells might be involved in the induction of inflammation in the late stage of abortion, but not in the early stage (Nakashima et al., 2010). "

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