title: Omega-6 docosapentaenoic acid-derived resolvins and 17-hydroxydocosahexaenoic acid modulate macrophage function and alleviate experimental colitis.
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).
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Hepatology, Gastroenterology and Endocrinology, Charité University Medicine Berlin, Campus Virchow Klinikum, Berlin, Germany.
authors.forename: Cheng-Ying
authors.initials: CY
authors.lastname: Chiu
authors.forename: Beate
authors.initials: B
authors.lastname: Gomolka
authors.forename: Cordula
authors.initials: C
authors.lastname: Dierkes
authors.forename: Nora R
authors.initials: NR
authors.lastname: Huang
authors.forename: Maik
authors.initials: M
authors.lastname: Schroeder
authors.forename: Martin
authors.initials: M
authors.lastname: Purschke
authors.forename: Dieter
authors.initials: D
authors.lastname: Manstein
authors.forename: Bindi
authors.initials: B
authors.lastname: Dangi
authors.forename: Karsten H
authors.initials: KH
authors.lastname: Weylandt
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology* / Q000627:therapeutic use; D002460:Cell Line; D003092:Colitis / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology; D004195:Disease Models, Animal; D004281:Docosahexaenoic Acids / Q000494:pharmacology* / Q000627:therapeutic use; D005231:Fatty Acids, Unsaturated / Q000494:pharmacology* / Q000627:therapeutic use; D008264:Macrophages / Q000187:drug effects* / Q000502:physiology; D051379:Mice; D010587:Phagocytosis / Q000187:drug effects
chemical_list: D000893:Anti-Inflammatory Agents; D005231:Fatty Acids, Unsaturated; D004281:Docosahexaenoic Acids; C062894:17-hydroxy-4,7,10,13,15,19-docosahexaenoic acid; C026219:docosapentaenoic acid