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

Tsukasa Ishida, Masaru Yoshida, Makoto Arita, Yosuke Nishitani, Shin Nishiumi, Atsuhiro Masuda, Shigeto Mizuno, Tetsuya Takagawa, Yoshinori Morita, Hiromu Kutsumi, Hideto Inokuchi, Charles N. Serhan, Richard S. Blumberg, Takeshi Azuma

研究成果: Article査読

128 被引用数 (Scopus)

抄録

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 proin-flammatory 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.

本文言語English
ページ(範囲)87-95
ページ数9
ジャーナルInflammatory bowel diseases
16
1
DOI
出版ステータスPublished - 2010 2月
外部発表はい

ASJC Scopus subject areas

  • 免疫アレルギー学
  • 消化器病学

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