Polyunsaturated Fatty Acids of Both the Omega-3 and the Omega-6 Family Abrogate the Cytokine-Induced Upregulation of miR-29a-3p by Endothelial Cells

Abstract

Cellular processes fundamentally depend on protein expression control. At this, protein expression is regulated on the transcriptional and the post-transcriptional level. PUFAs are already known to affect gene transcription. The present study was conducted to answer the question whether PUFAs are also able to impact on the miRNA-mediated post-transcriptional fine-tuning of mRNA copy numbers. To this end, cellular miRNA profiles were screened by means of next-generation sequencing and NanoString analysis to compare PUFA-enriched to unsupplemented endothelial cells exposed to an inflammatory milieu. Validation took place by droplet digital PCR, allowing for an absolute quantification of RNA copy numbers. The analyses revealed that the stimulation-induced upregulation of miR-29a-3p is blocked by PUFA enrichment of endothelial cells. What is more, mRNA copy numbers of miR-29a-3p targets, namely the coagulation factors PAI-1, TF, and vWF, as well as the proinflammatory cytokines IL-1β, IL-6, and IL-8, were reduced in PUFA-enriched endothelial cells compared to unsupplemented cells, counteracting the stimulatory effect of an inflammatory environment. These data hint toward a new mechanism of action by which PUFAs modulate the functionality of endothelial cells. Apparently, the inflammation-modulating properties of PUFAs are also mediated at the post-transcriptional level.

Maternal n-3 enriched diet reprograms neurovascular transcriptome and blunts inflammation in neonate

“…While traditionally n-3 PUFAs were believed to possess anti-inflammatory properties and n-6 PUFAs were considered to be purely pro-inflammatory, this concept has undergone modifications in recent years (Calder, 2006; Djuricic & Calder, 2021; Innes & Calder, 2018). For example, cell culture studies show that both n-3 and n-6 PUFAs can attenuate the baseline release of cytokines or promote/decrease the release of pro-inflammatory cytokines, or supress expression of adhesion molecule and coagulation factors after inflammatory stimulation (Hung et al, 2023; Maucher, Schmidt, Kuhlmann, & Schumann, 2020; Trommer, Leimert, Bucher, & Schumann, 2017). A recent study by Hellstrom et al reports association of higher DHA blood levels with lower severity of retinopathy of prematurity only when the level of AA in blood is sufficiently high (Hellstrom et al, 2021).…”

Mesoporous Silica Particles Functionalized with Newly Extracted Fish Oil (Omeg@Silica) Reducing IL-8 Counteract Cell Migration in NSCLC Cell Lines

“…In natural fish oil (i.e., not chemically refined, as is the case with most omega-3 food supplements), said PUFAs are present in triglyceride form. By significantly inhibiting tumour growth, suppressing cancer cell viability, and inducing apoptosis in various cancer cells, these essential lipids exert a therapeutic role against certain types of cancer [ 8 ], including lung cancer [ 9 , 10 ].…”