Gamma-linolenic acid inhibits inflammatory responses by regulating NF-kappaB and AP-1 activation in lipopolysaccharide-induced RAW 264.7 macrophages

Inflammation. 2010 Feb;33(1):46-57. doi: 10.1007/s10753-009-9157-8.


Gamma linolenic acid (GLA) is a member of the n-6 family of polyunsaturated fatty acids and can be synthesized from linoleic acid (LA) by the enzyme delta-6-desaturase. The therapeutic values of GLA supplementation have been documented, but the molecular mechanism behind the action of GLA in health benefits is not clear. In this study, we assessed the effect of GLA with that of LA on lipopolysaccharide (LPS)-induced inflammatory responses and further explored the molecular mechanism underlying the pharmacological properties of GLA in mouse RAW 264.7 macrophages. GLA significantly inhibited LPS-induced protein expression of inducible nitric oxide synthase, pro-interleukin-1beta, and cyclooxygenase-2 as well as nitric oxide production and the intracellular glutathione level. LA was less potent than GLA in inhibiting LPS-induced inflammatory mediators. Both GLA and LA treatments dramatically inhibited LPS-induced IkappaB-alpha degradation, IkappaB-alpha phosphorylation, and nuclear p65 protein expression. Moreover, LPS-induced nuclear factor-kappaB (NF-kappaB) and activator protein-1 (AP-1) nuclear protein-DNA binding affinity and reporter gene activity were significantly decreased by LA and GLA. Exogenous addition of GLA but not LA significantly reduced LPS-induced expression of phosphorylated extracellular signal-regulated kinase (ERK) 1/2 and c-Jun N-terminal kinase (JNK)-1. Our data suggest that GLA inhibits inflammatory responses through inactivation of NF-kappaB and AP-1 by suppressed oxidative stress and signal transduction pathway of ERK and JNK in LPS-induced RAW 264.7 macrophages.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / pharmacology*
  • Cell Line
  • Cell Survival / drug effects
  • Cyclooxygenase 2 / metabolism
  • Dose-Response Relationship, Drug
  • Glutathione / metabolism
  • I-kappa B Kinase / metabolism
  • Inflammation / immunology
  • Inflammation / metabolism
  • Inflammation / prevention & control*
  • Interleukin-1 / metabolism
  • Lipopolysaccharides / pharmacology*
  • Macrophages / drug effects*
  • Macrophages / immunology
  • Macrophages / metabolism
  • Mice
  • Mitogen-Activated Protein Kinase 1 / metabolism
  • Mitogen-Activated Protein Kinase 3 / metabolism
  • Mitogen-Activated Protein Kinase 8 / metabolism
  • Nitric Oxide / metabolism
  • Nitric Oxide Synthase Type II / metabolism
  • Phosphorylation
  • Protein Precursors / metabolism
  • RNA, Messenger / metabolism
  • Signal Transduction / drug effects
  • Transcription Factor AP-1 / genetics
  • Transcription Factor AP-1 / metabolism*
  • Transcription Factor RelA / genetics
  • Transcription Factor RelA / metabolism*
  • gamma-Linolenic Acid / pharmacology*


  • Anti-Inflammatory Agents
  • Interleukin-1
  • Lipopolysaccharides
  • Protein Precursors
  • RNA, Messenger
  • Rela protein, mouse
  • Transcription Factor AP-1
  • Transcription Factor RelA
  • interleukin 1 precursor
  • Nitric Oxide
  • gamma-Linolenic Acid
  • Nitric Oxide Synthase Type II
  • Nos2 protein, mouse
  • Ptgs2 protein, mouse
  • Cyclooxygenase 2
  • Chuk protein, mouse
  • I-kappa B Kinase
  • Mitogen-Activated Protein Kinase 1
  • Mitogen-Activated Protein Kinase 3
  • Mitogen-Activated Protein Kinase 8
  • Glutathione