Resolvin D۱ (Rvd۱) Attenuates In Vitro LPS-Stimulated Inflammation Through Downregulation of miR-۱۵۵, miR -۱۴۶, miR -۱۴۸ and Krupple Like Factor ۵

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 D۱ (RvD۱) is an endogenous omega-۳-derived lipid mediator with pro-resolving activity. This study aimed to evaluate the effect of Resolvin D۱ (RvD۱) on some inflammatory miRNAs (mir-۱۵۵-۵p, miR۱۴۶a-۵p and miR۱۴۸-۳p) and Krüppel-like factors ۵ (KLF۵) in an LPS-stimulated THP-۱ preclinical model of inflammation. Methods: PMA-differentiated THP-۱ cells (macrophages) were pre-incubated with or without various concentrations of RvD۱ (۱۰, ۵۰, or ۱۰۰ nM) for ۲ h prior to stimulation by ۱ μg/ml LPS. Un-stimulated PMA-differentiated THP-۱ 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 ۱ µg/ml LPS increased mRNA expression levels of TNF-α, KLF۵, miR-۱۵۵-۵p, miR-۱۴۶-۵p, and miR-۱۴۸a-۳p. When the cells were exposed to various concentrations (۱۰, ۵۰ and ۱۰۰ nM) of RvD۱ for ۲ h prior to LPS stimulation, the TNF-α, KLF۵, miR-۱۵۵-۵p, miR-۱۴۶-۵p, and miR-۱۴۸a-۳p mRNA expression levels were significantly downregulated in a dose-dependent manner, compared to the LPS group. Conclusion: The results demonstrate that RvD۱ can attenuate inflammatory response in LPS-stimulated macrophages. Our data also showed that RvD۱ may exert anti-inflammatory effects by inhibiting miR-۱۵۵-۵p, miR-۱۴۶a-۵p, and miR-۱۴۸-۳p.

کلیدواژه ها:

Chronic inflammation ، Krupple like factors (KLF) ، Micro-RNAs ، Resolvin D۱ (RvD۱) ، Macrophages.