Antagonistic Activity of Anandamide on Tat-treated Human Astrocytes Identifies Inflammaging Pathways: Anandamide Affects Aging Pathways.

PURPOSE: The endocannabinoid system can suppress inflammatory environment by regulating inflammatory mechanisms in immune and glial cells. Astrocytes secrete soluble inflammatory mediators. Prolonged activation of astrocytes is associated with accelerated aging in the central nervous system. MicroRNAs are increasingly shown to be critical gene regulators during inflammation and gliosis. In this study, we investigated the microRNA changes affected by anandamide (AEA), a dominant endocannabinoid in normal human astrocytes, following exposure to the HIV-1 Tat (Trans-activator of transcription) protein.

METHODS

We performed global human microRNA profiling in Tat-activated astrocytes on exposure to AEA. To delineate the mechanism of action, we utilized the bioinformatic tools miRWalk, KEGG, and Cytoscape to assess the global microarray data for significantly impacted miRNAs and their gene targets at the mRNA level.

RESULTS

Tat-induced activation significantly upregulated 122 miRNAs (P < 0.05) in astrocytes. Conversely, the addition of AEA in activated astrocytes significantly downregulated the expression of 57 miRNAs. Out of 122 miRNAs upregulated by Tat treatment, 37 miRNAs that were common to Tat and Tat+AEA cells showed reversed expression, suggesting these might be the critical miRNAs with a key role in the AEA-induced mitigation of neuroinflammation.

CONCLUSION

Reversed expression of a selected group of miRNAs identifies antagonistic pathways that promote an anti-inflammatory environment. Pathway analysis of these 37 key miRNAs showed gene targets that regulate inflammation and senescence.