Resolvin D1 (Rvd1) Attenuates In Vitro LPS-Stimulated Inflammation Through Downregulation of miR-155, miR -146, miR -148 and Krupple Like Factor 5.

ABSTRACT

Background: Chronic inflammation is associated with many inflammatory diseases. Specialized pro-resolving mediators (SPMs) are well known for their crucial role in promoting the resolution phase of inflammation and restoring tissue homeostasis. Resolvin D1 (RvD1) is an endogenous omega-3-derived lipid mediator with pro-resolving activity. This study aimed to evaluate the effect of Resolvin D1 (RvD1) on some inflammatory miRNAs (mir-155-5p, miR146a-5p and miR148-3p) and Krüppel-like factors 5 (KLF5) in an LPS-stimulated THP-1 preclinical model of inflammation. Methods: PMA-differentiated THP-1 cells (macrophages) were pre-incubated with or without various concentrations of RvD1 (10, 50, or 100 nM) for 2 h prior to stimulation by 1 µg/ml LPS. Un-stimulated PMA-differentiated THP-1 cells were as the control group. Then, the expression levels of target genes were evaluated by real-time PCR. Results: Compared with untreated macrophages, stimulation with 1 µg/ml LPS increased mRNA expression levels of TNF-α, KLF5, miR-155-5p, miR-146-5p, and miR-148a-3p. When the cells were exposed to various concentrations (10, 50 and 100 nM) of RvD1 for 2 h prior to LPS stimulation, the TNF-α, KLF5, miR-155-5p, miR-146-5p, and miR-148a-3p mRNA expression levels were significantly downregulated in a dose-dependent manner, compared to the LPS group. Conclusions: The results demonstrate that RvD1 can attenuate inflammatory response in LPS-stimulated macrophages. Our data also showed that RvD1 may exert anti-inflammatory effects by inhibiting miR-155-5p, miR-146a-5p, and miR-148-3p.