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


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-1?.

Methods and results

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

SUBMITTER: Zgorzynska E 

PROVIDER: S-EPMC7839194 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

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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.

Zgórzyńska Emilia E   Stulczewski Dawid D   Dziedzic Barbara B   Su Kuan-Pin KP   Walczewska Anna A  

BMC neuroscience 20210127 1


<h4>Background</h4>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 t  ...[more]

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