Omega-3 PUFAs Suppress IL-1β-Induced Hyperactivity of Immunoproteasomes in Astrocytes

• Main Authors: Emilia Zgorzynska, Barbara Dziedzic, Monika Markiewicz, Anna Walczewska
• Format: Article
• Language: English
• Published: MDPI AG 2021-05-01
• Series: International Journal of Molecular Sciences
• Subjects: immunoproteasome; astrocytes; C/EBPs; docosahexaenoic acid; eicosapentaenoic acid; connexin 43
• Online Access: https://www.mdpi.com/1422-0067/22/11/5410
• ISSN: 1661-6596; 1422-0067

The role of immunoproteasome (iP) in astroglia, the cellular component of innate immunity, has not been clarified. The results so far indicate that neuroinflammation, a prominent hallmark of Alzheimer’s disease, strongly activates the iP subunits expression. Since omega-3 PUFAs possess anti-inflammatory and pro-resolving activity in the brain, we investigated the effect of DHA and EPA on the gene expression of constitutive (β1 and β5) and inducible (iβ1/LMP2 and iβ5/LMP7) proteasome subunits and proteasomal activity in IL-1β-stimulated astrocytes. We found that both PUFAs downregulated the expression of IL-1β-induced the iP subunits, but not the constitutive proteasome subunits. The chymotrypsin-like activity was inhibited in a dose-dependent manner by DHA, and much strongly in the lower concentration by EPA. Furthermore, we established that C/EBPα and C/EBPβ transcription factors, being the <i>cis</i>-regulatory element of the transcription complex, frequently activated by inflammatory mediators, participate in a reduction in the iP subunits’ expression. Moreover, the expression of connexin 43 the major gap junction protein in astrocytes, negatively regulated by IL-1β was markedly increased in PUFA-treated cells. These findings indicate that omega-3 PUFAs attenuate inflammation-induced hyperactivity of iPs in astrocytes and have a beneficial effect on preservation of interastrocytic communication by gap junctions.