MiR-200c-3p inhibits LPS-induced M1 polarization of BV2 cells by targeting RIP2

• Published in: Genes & genomics Vol. 44; no. 4; pp. 477 - 486
• Main Authors: Zhao, Lei, Liu, Xiaosong, Yang, Jiankai, Wang, Xiaoliang, Liu, Xiaomeng, Wu, Jianliang, Li, Chen, Xu, Donggang, Hu, Yuhua
• Format: Journal Article
• Language: English
• Published: Singapore Springer Singapore 01.04.2022; Springer; Springer Nature B.V; 한국유전학회
• Subjects: Animal Genetics and Genomics; Biomedical and Life Sciences; Cell activation; Chromosome 3; Cytokines; Cytokines - genetics; Cytokines - metabolism; Human Genetics; Inflammation; Interleukin 6; Life Sciences; Lipopolysaccharides; Lipopolysaccharides - pharmacology; Luciferase; Major histocompatibility complex; Microbial Genetics and Genomics; Microglia; MicroRNA; MicroRNAs - metabolism; miRNA; NF-kappa B - genetics; NF-kappa B - metabolism; NF-κB protein; Nitric oxide; Nitric-oxide synthase; Nuclear transport; Phenotypes; Phosphorylation; Plant Genetics and Genomics; Polarization; Research Article; Therapeutic targets; Tumor Necrosis Factor-alpha - metabolism; Tumor necrosis factor-TNF; Tumor necrosis factor-α; 생물학; LPS treatment; miR-200c-3p; Microglia activation; RIP2
• ISSN: 1976-9571; 2092-9293
• DOI: 10.1007/s13258-021-01210-z

Background Microglia are important immune cells, which can be induced by lipopolysaccharide (LPS) into M1 phenotype that express pro-inflammatory cytokines. Some studies have shown that microRNAs play critical roles in microglial activation. Objective This study was designed to investigate the role of miR-200c-3p in regulating inflammatory responses of LPS-treated BV2 cells. Methods The expression of miR-200c-3p in BV2 cells was detected by real-time PCR. Receptor-interacting protein 2 (RIP2) was predicted as a target gene of miR-200c-3p. Their relationship was verified by dual-luciferase reporter assay. The function of miR-200c-3p and RIP2 in microglial polarization and NF-κB signaling was further evaluated. Results LPS treatment reduced miR-200c-3p expression in a dose-dependent and time-dependent manner in BV2 cells. LPS treatment increased the expression of M1 phenotype markers inducible nitric oxide synthase (iNOS) and major histocompatibility complex class (MHC)-II, promoted the release of pro-inflammatory cytokines interleukin (IL)-1β, IL-6 and tumor necrosis factor (TNF)-α, and enhanced the nuclear translocation and phosphorylation of nuclear factor-kappaB (NF-κB) p65. Reversely, miR-200c-3p mimics down-regulated the levels of these inflammatory factors. Furthermore, RIP2 was identified to be a direct target of miR-200c-3p. RIP2 knockdown had a similar effect to miR-200c-3p mimics. Overexpression of RIP2 eliminated the inhibitory effect of miR-200c-3p on LPS-induced M1 polarization and NF-κB activation in BV2 cells. Conclusions MiR-200c-3p mimics suppressed LPS-induced microglial M1 polarization and NF-κB activation by targeting RIP2. MiR-200c-3p/RIP2 might be a potential therapeutic target for the treatment of neuroinflammation-associated diseases.