Phospholipid Incorporation of Non-Methylene-Interrupted Fatty Acids (NMIFA) in Murine Microglial BV-2 Cells Reduces Pro-Inflammatory Mediator Production

Inflammation. 2015 Dec;38(6):2133-45. doi: 10.1007/s10753-015-0196-z.

Abstract

Sciadonic acid (SCA), pinolenic acid (PNA), and Δ7-eicosatrienoic acid (Δ7-ETrA) are three non-methylene-interrupted fatty acids (NMIFA). Using murine microglial BV-2 cells, this study determined how NMIFA incorporation modulated phospholipid fatty acid composition and the production of pro-inflammatory mediators. Each NMIFA was rapidly taken up and incorporated in BV-2 cells, resulting in the differential redistribution of total lipids. The cellular phospholipid fatty acid compositions were altered, and a significant decrease in the proportions of total monounsaturated fatty acids (MUFA) was observed while the proportions of NMIFA and its metabolites accounted for 38% of the fatty acid total. Incubation of microglial cells with NMIFA suppressed production of LPS-stimulated pro-inflammatory mediators, including nitric oxide (NO), prostaglandin E2 (PGE2), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α), as well as the over-expression of inducible nitric oxide synthase (iNOS) and type 2 cyclooxygenase (COX-2). These inhibitory effects could be accounted for, in part, by the inactivation of mitogen-activated protein kinases (MAPK) signaling. In conclusion, Δ7-ETrA, PNA, and SCA are anti-inflammatory NMIFA that may be useful in suppressing in vitro immune responses involved in neural inflammation.

Keywords: inflammation; microglial cells; non-methylene-interrupted fatty acids (NMIFA); pinolenic acid (PNA); sciadonic acid (SCA); Δ7-eicosatrienoic acid (Δ7-ETrA).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / metabolism
  • Anti-Inflammatory Agents / pharmacology*
  • Arachidonic Acids / metabolism
  • Arachidonic Acids / pharmacology*
  • Cell Line
  • Cyclooxygenase 2 / metabolism
  • Dinoprostone / metabolism
  • Dose-Response Relationship, Drug
  • Down-Regulation
  • Enzyme Activation
  • Fatty Acids, Monounsaturated / metabolism
  • Fatty Acids, Monounsaturated / pharmacology*
  • Inflammation Mediators / immunology
  • Inflammation Mediators / metabolism*
  • Interleukin-6 / metabolism
  • Linolenic Acids / metabolism
  • Linolenic Acids / pharmacology*
  • MAP Kinase Signaling System / drug effects
  • Mice
  • Microglia / drug effects*
  • Microglia / immunology
  • Microglia / metabolism
  • Mitogen-Activated Protein Kinases / metabolism*
  • Nitric Oxide / metabolism
  • Nitric Oxide Synthase Type II / metabolism
  • Phospholipids / metabolism*
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Anti-Inflammatory Agents
  • Arachidonic Acids
  • Fatty Acids, Monounsaturated
  • Inflammation Mediators
  • Interleukin-6
  • Linolenic Acids
  • Phospholipids
  • Tumor Necrosis Factor-alpha
  • interleukin-6, mouse
  • 5,9,12-octadecatrienoic acid
  • Nitric Oxide
  • eicosa-5,11,14-trienoic acid
  • Nitric Oxide Synthase Type II
  • Nos2 protein, mouse
  • Ptgs2 protein, mouse
  • Cyclooxygenase 2
  • Mitogen-Activated Protein Kinases
  • Dinoprostone
  • eicosenoic acid