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Resveratrol Protects Against Pathological Preterm Birth by Suppression of Macrophage-Mediated Inflammation

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Abstract

Inflammatory cytokines play a major role in spontaneous preterm birth. Resveratrol has strong anti-inflammatory effects, but its effect on preterm birth in vivo is unknown. We investigated whether resveratrol protects against preterm birth in the lipopolysaccharide (LPS)-induced preterm mouse model. Twelve-day-old pregnant mice were fed 20 to 40 mg/kg resveratrol daily. On day 15, 10 μg of LPS was injected into uterine cervices. Resveratrol administration significantly decreased the rate of preterm birth. Resveratrol administration abolished LPS-induced elevation of tumor necrosis factor α (TNF-α) and interleukin (IL) 1β but not IL-6 levels. The TNF-α messenger RNA levels were decreased in the cervices of resveratrol-administered mice compared with controls. Resveratrol treatment suppressed the elevation in TNF-α and IL-1β levels in LPS-exposed peritoneal macrophages. Further resveratrol treatment eradicated the proinflammatory cytokine-mediated elevation in cyclooxygenase 2 (COX-2) in peritoneal macrophages. Resveratrol may protect against pathological preterm birth by suppression of elevated proinflammatory cytokines and consequent elevation of COX-2 in macrophages.

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Authors and Affiliations

  1. Department of Obstetrics and Gynecology, Graduate School of Medicine, Faculty of Medicine, The University of Tokyo, 7-3-1 Hongo, 113-8655, Bunkyo-ku, Tokyo, Japan

    Hitomi Furuya MD, Ayumi Taguchi MD, Kei Kawana MD, PhD, Aki Yamashita MD, PhD, Eri Inoue MD, Mitsuyo Yoshida MD, Hiroe Nakamura MD, Asaha Fujimoto MD, Tomoko Inoue MD, Masakazu Sato MD, Haruka Nishida MD, Kazunori Nagasaka MD, PhD, Katsuyuki Adachi MD, PhD, Mari Hoya MD, Takeshi Nagamatsu MD, PhD, Osamu Wada-Hiraike MD, PhD, Takahiro Yamashita MD, PhD, Yutaka Osuga MD, PhD & Tomoyuki Fujii MD, PhD

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  1. Hitomi Furuya MD
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  2. Ayumi Taguchi MD
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  3. Kei Kawana MD, PhD
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  4. Aki Yamashita MD, PhD
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  15. Takeshi Nagamatsu MD, PhD
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  16. Osamu Wada-Hiraike MD, PhD
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Correspondence to Kei Kawana MD, PhD.

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Furuya, H., Taguchi, A., Kawana, K. et al. Resveratrol Protects Against Pathological Preterm Birth by Suppression of Macrophage-Mediated Inflammation. Reprod. Sci. 22, 1561–1568 (2015). https://doi.org/10.1177/1933719115589413

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