Omega-3 Polyunsaturated Fatty Acids To Achieve The Regulation Of Inflammation By Affecting The Expression Of MiR-146b

Objective MicroRNAs (miRNAs) are small endogenous non-coding RNAs involved in post transcriptional gene regulation that have crucial roles in several types of tissues. Polyunsaturated fatty acids (PUFAs) are dietary factors that have potential ability to facilitate reduction inflammation and maintain immune homeostasis. Our aim is to determine the roles and mechanisms of microRNA in PUFA-modulated immune homeostasis pathways in this paper.Methods Three-week-old Wistar rats were separated and treated by Omega-3diet and Omega-6diet respectively to build PUFA diet-induced autoimmune (AI)-prone and AI-averse rat models. Flow cytometry and ELISA assay was conducted to determine the immune state of rats. MiRNA microarray assays and RT-qPCR tests was performed to screen the PUFA-modulated miRNAs. Computational analysis was preferred to selecet the miRNAs involved in inflammatory biological pathways. Luciferase reporter assay and microRNA sponge was used to confirm the regulatory roles of PUFA-modulated miRNAs.Results We compared physical signs and immune statuses of PUFA-treated rats. The results show that omega-3PUFAs decreased pro-inflammatory cytokines such as interleukin-6(IL-6), C-reactive protein (CRP), and tumor necrosis factor-alpha (TNF-a), and increased CD8+suppressor T cells and regulatory T cells (Tregs) in rats. Candidate miRNAs in peripheral serum were filtered by microarray assay, and validated in PUFA metabolism-related tissues by real-time quantitative-PCR (RT-qPCR) after the establishment of PUFA diet-induced AI-prone and AI-averse rat models. Biological database and computational algorithms were used to identify the validated targeted genes of PUFA-modulated miRNA, which may play key roles in many immune system pathways. Luciferase reporter assay confirmed the direct binding of miR-146b on the Smad4mRNA’s3’UTR. MicroRNA sponge of miR-146b significantly increased Smad4levels in the rat adipocytes.Conclusion These findings provide in vivo evidence that the PUFA-regulated miRNAs play significant roles in modulation of immune homeostasis. Omega-3PUFAs can exert their anti-inflammatory function by modulate TGF-β signal transduction via miRNAs in adipocytes of rats.