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

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-alpha and IL-12p40. In HEK293 cells, pretreatment with RvE1 inhibited TNF-alpha-induced nuclear translocation of NF-kappaB 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.

• Authors: 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
• Journal: Inflammatory bowel diseases (Inflamm Bowel Dis) Vol. 16 Issue 1 Pg. 87-95 (Jan 2010) ISSN: 1536-4844 [Electronic] England
• PMID: 19572372 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Inflammation Mediators
• NF-kappa B
• RNA, Messenger
• Receptors, Chemokine
• Dextran Sulfate
• Eicosapentaenoic Acid
• 5S,12R,18R-trihydroxy-6Z,8E,10E,14Z,16E-eicosapentaenoic acid

Topics

• Animals
• Cell Nucleus (metabolism)
• Cells, Cultured
• Colitis (chemically induced, immunology, prevention & control)
• Dextran Sulfate (toxicity)
• Eicosapentaenoic Acid (analogs & derivatives, pharmacology)
• Female
• Flow Cytometry
• Humans
• Immunoenzyme Techniques
• Inflammation (immunology, pathology, prevention & control)
• Inflammation Mediators (metabolism)
• Kidney (cytology, metabolism)
• Macrophages, Peritoneal (drug effects, immunology, pathology)
• Mice
• Mice, Inbred C57BL
• NF-kappa B (genetics, metabolism)
• Protein Transport
• RNA, Messenger (genetics, metabolism)
• Receptors, Chemokine (metabolism)
• Reverse Transcriptase Polymerase Chain Reaction