Docosapentaenoic Acid (22:5n-3) Downregulates mRNA Expression of Pro-inflammatory Factors in LPS-activated Murine Macrophage Like RAW264.7 Cells

J Oleo Sci. 2017 Oct 1;66(10):1149-1156. doi: 10.5650/jos.ess17111. Epub 2017 Sep 15.

Abstract

Docosapentaenoic acid (22:5n-3, n-3 DPA) is a n-3 polyunsaturated fatty acid (PUFA) found in fish oil, and has been reported to have health benefits. This study investigated conversion of n-3 DPA, and examined the anti-inflammatory effects of n-3 DPA on activated macrophages. Murine macrophage-like RAW264.7 cells were incubated in culture media containing n-3 DPA for 72 h. The level of n-3 DPA in the fatty acid composition of the total lipid fraction increased in a dose-dependent manner. Furthermore, the levels of docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) were higher in treated cells than in control cells. In RAW264.7 cells stimulated by lipopolysaccharide (LPS), n-3 DPA significantly down-regulated mRNA expression of pro-inflammatory factors such as IL-6, IL-1β, iNOS and COX-2. Production of IL-6 was also reduced by n-3 DPA in a dose-dependent manner. We found that n-3 DPA treatment resulted in greater IL-6 mRNA down-regulation than that achieved with EPA treatment, and was similar to that of DHA treatment. Furthermore, expression levels of IL-6 and IL-1β mRNAs were measured in the presence of the delta-6 desaturase inhibitor SC26196 in the culture medium to inhibit the conversion of n-3 DPA to DHA. There was no significant difference in the down-regulation in the mRNA expression of pro-inflammatory cytokines in RAW264.7 cells by n-3 DPA with or without presence of SC26196. These results demonstrate that n-3 DPA exhibits anti-inflammatory effects in activated RAW264.7 cells, which are independent of DHA conversion.

Keywords: anti-inflammation; cytokine; macrophage; n-3 docosapentaenoic acid; n-3 polyunsaturated fatty acids.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents*
  • Cyclooxygenase 2 / genetics
  • Cyclooxygenase 2 / metabolism
  • Dose-Response Relationship, Drug
  • Down-Regulation / drug effects*
  • Fatty Acids, Unsaturated / metabolism
  • Fatty Acids, Unsaturated / pharmacology*
  • Gene Expression / drug effects*
  • Gene Expression / genetics*
  • Inflammation Mediators / metabolism*
  • Interleukin-1beta / genetics*
  • Interleukin-1beta / metabolism*
  • Interleukin-6 / genetics*
  • Interleukin-6 / metabolism*
  • Lipopolysaccharides / immunology*
  • Macrophage Activation / genetics*
  • Macrophage Activation / immunology*
  • Mice
  • Nitric Oxide Synthase Type II / genetics
  • Nitric Oxide Synthase Type II / metabolism
  • RAW 264.7 Cells
  • RNA, Messenger / genetics*
  • RNA, Messenger / metabolism*

Substances

  • Anti-Inflammatory Agents
  • Fatty Acids, Unsaturated
  • Inflammation Mediators
  • Interleukin-1beta
  • Interleukin-6
  • Lipopolysaccharides
  • RNA, Messenger
  • Nitric Oxide Synthase Type II
  • Cyclooxygenase 2
  • docosapentaenoic acid