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Omega-6 docosapentaenoic acid-derived resolvins and 17-hydroxydocosahexaenoic acid modulate macrophage function and alleviate experimental colitis

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An Erratum to this article was published on 14 September 2012

Abstract

Objective

Enzymatically oxygenated lipid products derived from omega-3 and omega-6 fatty acids play an important role in inflammation dampening. This study examined the anti-inflammatory effects of n-6 docosapentaenoic acid-derived (17S)-hydroxy-docosapentaenoic acid (17-HDPAn-6) and (10,17S)-dihydroxy-docosapentaenoic acid (10,17-HDPAn-6) as well as n-3 docosahexaenoic acid-derived 17(R/S)-hydroxy-docosahexaenoic acid (17-HDHA).

Materials and methods

The effects of 17-HDPAn-6, 10,17-HDPAn-6 or 17-HDHA on activity and M1/M2 polarization of murine macrophage cell line RAW 264.7 were examined by phagocytosis assay and real-time PCR. To assess anti-inflammatory effects in vivo, dextran sodium sulfate (DSS) colitis was induced in mice treated with 17-HDPAn-6, 10,17-HDPAn-6, 17-HDHA or NaCl.

Results

Our results show that 17-HDPAn-6, 10,17-HDPAn-6 and 17-HDHA increase phagocytosis in macrophages in vitro and promote polarization towards the anti-inflammatory M2 phenotype with decreased gene expression of TNF-α and inducible Nitric oxide synthase and increased expression of the chemokine IL-1 receptor antagonist and the Scavenger receptor Type A. Intraperitoneal treatment with 17-HDPAn-6, 10,17-HDPAn-6, or 17-HDHA alleviated DSS-colitis and significantly improved body weight loss, colon epithelial damage, and macrophage infiltration.

Conclusion

These results suggest that DPAn-6-derived 17-HDPAn-6 and 10,17-HDPAn-6 as well as the DHA-derived 17-HDHA have inflammation-dampening and resolution-promoting effects that could be used to treat inflammatory conditions such as inflammatory bowel disease.

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Acknowledgments

17-HDPA and 10,17-HDPA were provided by Martek Biosciences (a division of DSM Nutritional Products). K.H.W. is supported by the German Research Fund (DFG) and Charité intramural research funds. Part of the research work presented here was funded by Martek Biosciences. C.Y.C. was supported by a grant from the German Academic Exchange Service (Biomedical Sciences Exchange Program).

Author information

Authors and Affiliations

  1. Department of Hepatology, Gastroenterology and Endocrinology, Charité University Medicine Berlin, Campus Virchow Klinikum, Berlin, Germany

    Cheng-Ying Chiu, Beate Gomolka, Cordula Dierkes, Nora R. Huang, Maik Schroeder & Karsten H. Weylandt

  2. Laboratory for Lipid Medicine and Technology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA

    Cheng-Ying Chiu, Nora R. Huang & Karsten H. Weylandt

  3. Wellman Center of Photomedicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA

    Martin Purschke & Dieter Manstein

  4. DSM Nutritional Products, Columbia, MD, USA

    Bindi Dangi

  5. Med. Klinik m. S. Gastroenterologie and Hepatologie, Charité Campus Virchow Hospital, Augustenburger Platz 1, Berlin, 13353, Germany

    Karsten H. Weylandt

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  1. Cheng-Ying Chiu
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  2. Beate Gomolka
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Correspondence to Karsten H. Weylandt.

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Chiu, CY., Gomolka, B., Dierkes, C. et al. Omega-6 docosapentaenoic acid-derived resolvins and 17-hydroxydocosahexaenoic acid modulate macrophage function and alleviate experimental colitis. Inflamm. Res. 61, 967–976 (2012). https://doi.org/10.1007/s00011-012-0489-8

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