Docosahexaenoic fatty acid reduces the pro-inflammatory response induced by IL-1β in astrocytes through inhibition of NF-κB and AP-1 transcription factor activation

BMC Neurosci. 2021 Jan 27;22(1):4. doi: 10.1186/s12868-021-00611-w.

Abstract

Background: Astrocytes are responsible for a broad range of functions that maintain homeostasis in the brain. However, their response to the pro-inflammatory cytokines released by activated microglia in various neurological pathologies may exacerbate neurodegenerative processes. Accumulating evidence suggests that omega-3 docosahexaenoic fatty acid (DHA) has an anti-inflammatory effect in various cell cultures studies and in a variety of neurological disorders. In this study we examined the mechanism involved in the inhibition of the pro-inflammatory response by DHA in astrocytes treated with IL-1β.

Methods and results: Activation of the transcription factors NF-κB and AP-1 was measured in IL-1β-treated primary astrocytes incubated with various concentrations of DHA. COX-2 and iNOS protein expression was determined by Western blot, and TNF-α and IL-6 secretion was measured using ELISA-based assays. DHA treatment inhibited translocation of p65NF-κB to the nucleus, significantly lowered p65NF-κB protein level and fluorescence of p65NF-κB in the nucleus, reduced dose-dependently IκB protein phosphorylation, and the binding of the AP-1 transcription factor members (c-Jun/c-Fos) to the specific TPA-response element (TRE) of DNA. In addition, the expression of pro-inflammatory COX-2 and iNOS proteins was downregulated and TNF-α and IL-6 secretion was also reduced.

Conclusions: These results indicate that DHA is a powerful factor that reduces the pro-inflammatory response in astrocytes. Consequently, successful introduction of DHA into the astrocyte membranes can attenuate neuroinflammation, which is a key factor of age-related neurodegenerative disorders.

Keywords: Astrocytes; Docosahexaenoic acid; Neuroinflammation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / pharmacology*
  • Astrocytes / drug effects
  • Astrocytes / metabolism*
  • Docosahexaenoic Acids / pharmacology*
  • Inflammation / metabolism
  • Interleukin-1beta / metabolism
  • NF-kappa B / metabolism*
  • Rats
  • Transcription Factor AP-1 / metabolism*

Substances

  • Anti-Inflammatory Agents
  • Interleukin-1beta
  • NF-kappa B
  • Transcription Factor AP-1
  • Docosahexaenoic Acids