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Resolvin D1 Promotes SIRT1 Expression to Counteract the Activation of STAT3 and NF-κB in Mice with Septic-Associated Lung Injury

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Abstract

Resolvin D1 (RvD1) is a novel endogenous docosahexaenoic acid (DHA)-derived lipid mediators, which possesses a dual role of anti-inflammation and promotes inflammation resolution. The aim of the present study was to assess the effects of RvD1 on cecal ligation and puncture (CLP) model of sepsis and explore the underlying mechanism. Six-to-eight-week-old male C57BL/6 mice were randomly divided into following three groups: sham-operated group (SO), CLP model group (CLP), and CLP+RvD1 group (RvD1). The SO group underwent the sham operation. The RvD1 groups were administered RvD1 (10-ng/g body weight) by penile vein injection, but the CLP groups were administered the same volume of vehicle (PBS) after CLP. We assessed the survival benefit of RvD1 in CLP-induced septic mice for 7 days. After 24 h, mice were sacrificed, bronchoalveolar lavage fluids (BALF) was collected for proinflammatory cytokines assay, and albumin assay and the lung tissues were harvested for histologic analysis, myeloperoxidase (MPO) activity and the expression of Sirtuin 1 (SIRT1), signal transducers, and activators of transcription 3 (STAT3), nuclear factor-κB (NF-κB), and mitogen-activated protein kinases (MAPKs). RvD1 treatment increased the survival time in mice with sepsis induced by CLP, reducing the MPO activity and albumin level at 24 h. The levels of inflammatory cytokines, including tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), and interleukin-6 (IL-6) in BALF were significantly decreased by RvD1. RvD1 promoted SIRT1 expression and suppressed the activation of NF-κB, STAT3, ERK, and p38 in lung tissues of septic mice. These results suggest that RvD1 may improve survival and attenuate the degree of lung inflammation reaction in mice with CLP by suppressing STAT3, NF-κB, ERK, and p38 expressions through a mechanism partly dependent on SIRT1.

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Funding

This work is supported by Tianjin Science and Technology Project, China, No.13RCGFSY19300.

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Authors and Affiliations

  1. Department of Cell and Molecular Biology, Institute of Acute Abdominal Diseases of Integrated Traditional Chinese and Western Medicine, Tianjin Nankai Hospital, Tianjin, 300100, China

    Yuzhen Zhuo, Shukun Zhang, Caixia Li & Lei Yang

  2. Center for Experimental Therapeutics and Reperfusion Injury, Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, 02115, USA

    Hongwei Gao

  3. Department of Surgery, Tianjin Nankai Hospital, Tianjin, 300100, China

    Ximo Wang

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  1. Yuzhen Zhuo
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  2. Shukun Zhang
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  3. Caixia Li
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  5. Hongwei Gao
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  6. Ximo Wang
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Correspondence to Hongwei Gao or Ximo Wang.

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Zhuo, Y., Zhang, S., Li, C. et al. Resolvin D1 Promotes SIRT1 Expression to Counteract the Activation of STAT3 and NF-κB in Mice with Septic-Associated Lung Injury. Inflammation 41, 1762–1771 (2018). https://doi.org/10.1007/s10753-018-0819-2

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