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

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-1 beta. Methods and results Activation of the transcription factors NF-kappa B and AP-1 was measured in IL-1 beta-treated primary astrocytes incubated with various concentrations of DHA. COX-2 and iNOS protein expression was determined by Western blot, and TNF-alpha and IL-6 secretion was measured using ELISA-based assays. DHA treatment inhibited translocation of p65NF-kappa B to the nucleus, significantly lowered p65NF-kappa B protein level and fluorescence of p65NF-kappa B in the nucleus, reduced dose-dependently I kappa B 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-alpha 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.