Resolvin E1, an endogenous lipid mediator derived from eicosapentaenoic acid, prevents dextran sulfate sodium–induced colitis

Authors

  • Tsukasa Ishida MD,

    1. Division of Gastroenterology, Department of Internal Medicine, Graduate School of Medicine, Kobe University, Kobe, Japan
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  • Masaru Yoshida MD, PhD,

    Corresponding author
    1. Division of Gastroenterology, Department of Internal Medicine, Graduate School of Medicine, Kobe University, Kobe, Japan
    2. Integrated Center for Mass Spectrometry, Graduate School of Medicine, Kobe University, Kobe, Japan
    • Division of Gastroenterology, Department of Internal Medicine, Graduate School of Medicine, Kobe University, 7-5-1, Chuo-ku, Kusunoki-cho, Kobe, Hyogo, 650-0017, Japan
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  • Makoto Arita PhD,

    1. Department of Health Chemistry, Graduate School of Pharmaceutical Sciences, Tokyo University, Tokyo, Japan
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  • Yosuke Nishitani PhD,

    1. Organization of Advanced Science and Technology, Kobe University, Kobe, Japan
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  • Shin Nishiumi PhD,

    1. Division of Gastroenterology, Department of Internal Medicine, Graduate School of Medicine, Kobe University, Kobe, Japan
    2. Integrated Center for Mass Spectrometry, Graduate School of Medicine, Kobe University, Kobe, Japan
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  • Atsuhiro Masuda MD, PhD,

    1. Division of Gastroenterology, Department of Internal Medicine, Graduate School of Medicine, Kobe University, Kobe, Japan
    2. Department of Medical Pharmaceutics, Kobe Pharmaceutical University, Kobe, Japan
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  • Shigeto Mizuno MD, PhD,

    1. Department of Medical Pharmaceutics, Kobe Pharmaceutical University, Kobe, Japan
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  • Tetsuya Takagawa MD, PhD,

    1. Division of Gastroenterology, Department of Internal Medicine, Graduate School of Medicine, Kobe University, Kobe, Japan
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  • Yoshinori Morita MD, PhD,

    1. Division of Gastroenterology, Department of Internal Medicine, Graduate School of Medicine, Kobe University, Kobe, Japan
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  • Hiromu Kutsumi MD, PhD,

    1. Division of Gastroenterology, Department of Internal Medicine, Graduate School of Medicine, Kobe University, Kobe, Japan
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  • Hideto Inokuchi MD, PhD,

    1. Division of Gastroenterology, Department of Internal Medicine, Graduate School of Medicine, Kobe University, Kobe, Japan
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  • Charles N. Serhan PhD,

    1. Department of Anesthesiology, Perioperative, and Pain Medicine, Center for Experimental Therapeutics and Reperfusion Injury, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts
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  • Richard S. Blumberg MD, PhD,

    1. Division of Gastroenterology, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts
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  • Takeshi Azuma MD, PhD

    1. Division of Gastroenterology, Department of Internal Medicine, Graduate School of Medicine, Kobe University, Kobe, Japan
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Abstract

Background:

Resolvin E1 (RvE1), an endogenous lipid mediator derived from eicosapentaenoic acid, has been identified in local inflammation during the healing stage. RvE1 reduces inflammation in several types of animal models including peritonitis and retinopathy and blocks human neutrophil transendothelial cell migration. The RvE1 receptor ChemR23 is expressed on myeloid cells such as macrophages and dendritic cells. The aim of this study was to determine whether RvE1 regulates colonic inflammation when the innate immune response of macrophages plays a key role in pathogenesis and tissue damage.

Methods:

The RvE1 receptor ChemR23 was expressed in mouse peritoneal macrophages as defined by flow cytometry. Peritoneal macrophages were pretreated with RvE1, followed by lipopolysaccharide stimulation, whereupon transcriptional levels of proinflammatory cytokines were analyzed.

Results:

RvE1 treatment led to inhibition of proinflammatory cytokines including TNF-α and IL-12p40. In HEK293 cells, pretreatment with RvE1 inhibited TNF-α-induced nuclear translocation of NF-κB in a ChemR23-dependent manner. These results suggested that RvE1 could regulate proinflammatory responses of macrophages expressing ChemR23. Therefore, we investigated the beneficial effects of RvE1 in dextran sulfate sodium–induced colitis. RvE1 treatment led to amelioration of colonic inflammation.

Conclusions:

These results indicate that RvE1 suppresses proinflammatory responses of macrophages. RvE1 and its receptor may therefore be useful as therapeutic targets in the treatment of human inflammatory bowel disease and other inflammatory disorders. Inflamm Bowel Dis 2010

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