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Hakan Cakmak, Frederick Schatz, S.-T. Joseph Huang, Lynn Buchwalder, Mizanur Rahman, Aydin Arici, Charles J. Lockwood, Progestin Suppresses Thrombin- and Interleukin-1β-Induced Interleukin-11 Production in Term Decidual Cells: Implications for Preterm Delivery, The Journal of Clinical Endocrinology & Metabolism, Volume 90, Issue 9, 1 September 2005, Pages 5279–5286, https://doi.org/10.1210/jc.2005-0210
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Abstract
Context: Decidual inflammation and hemorrhage are major contributors to the pathogenesis of preterm delivery (PTD). IL-11 is a cytokine with pleiotropic biological effects, including induction of T helper cell type 2 and inhibition of T helper cell type 1 cytokine responses. Paradoxically, it enhances the synthesis of prostaglandins, which induce labor.
Objective: The objectives of this study were to evaluate in vivo IL-11 expression in decidua after term and preterm deliveries and evaluate the effects of the primary mediators of inflammation, IL-1β and TNF-α, as well as the primary regulator of hemostasis, thrombin, on IL-11 expression in cultured term decidual cells (DCs).
Interventions and Main Outcome Measures: Human decidua from uncomplicated term deliveries and chorioamnionitis- or placental abruption-related PTDs were immunostained for IL-11. Cultures of DCs were primed with estradiol (E2) or with E2 and medroxyprogesterone acetate (MPA), then incubated in a defined medium with corresponding steroid(s) with or without IL-1β, TNF-α, or thrombin. IL-11 levels in DC-defined media were assessed by ELISA and Western blotting; IL-11 mRNA levels were measured by quantitative RT-PCR.
Results: IL-11 immunostaining was significantly higher in DCs after PTD compared with those after term delivery (P < 0.05). In the absence of cytokines or thrombin, IL-11 levels in the defined medium were 47% lower in incubations with E2 plus MPA vs. E2 alone (P = 0.001). IL-1β and thrombin elevated IL-11 output during incubations with E2 [24-fold (P < 0.05) and 120-fold (P < 0.05), respectively]. These increases were blunted by the addition of MPA [13-fold (P < 0.05) and 36-fold (P < 0.05), respectively]. Western blot analysis confirmed the ELISA results, and RT-PCR demonstrated corresponding effects on IL-11 mRNA levels. Unexpectedly, TNF-α did not affect IL-11 levels.
Conclusion: Because excess IL-1β and thrombin generation are associated with chorioamnionitis- and abruption-related PTD, respectively, these findings add to our understanding of the genesis of inflammation- and abruption-associated prematurity.
