Dataset Information

MiR-146a activates WAVE2 expression and enhances phagocytosis in lipopolysaccharide-stimulated RAW264.7 macrophages.

ABSTRACT: MiR-146a has been shown to play a critical role in cell immunity and phagocytosis, processes that require rearrangement of the cytoskeleton. However, the detailed mechanism by which miR-146a regulates these events remains elusive. Here, we used luciferase reporter and protein assays to show that the cytoskeleton-regulatingprotein verprolin-homologous protein 2 (WAVE2), is a direct target of miR-146a. MiR-146a overexpression resulted in a decrease in WAVE2 protein expression under endotoxin-free culture conditions. Unexpectedly, however, miR-146a activated rather than repressed the expression of WAVE2 in macrophage RAW264.7 cells when cultured continuously in the presence of endotoxin. Furthermore, we demonstrated that miR-146a induced WAVE2 expression and enhanced phagocytosis in lipopolysaccharide-stimulated RAW264.7 macrophages. Our study suggests that lipopolysaccharide- induced miR146a indirectly activates WAVE2 expression; thus, facilitating cytoskeletal reorganization and phagocytosis in lipopolysaccharide-stimulated macrophages.

SUBMITTER: Cao Z

PROVIDER: S-EPMC4568802 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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MiR-146a activates WAVE2 expression and enhances phagocytosis in lipopolysaccharide-stimulated RAW264.7 macrophages.

Cao Zhongwei Z Yao Qunyan Q Zhang Shuncai S

American journal of translational research 20150815 8

MiR-146a has been shown to play a critical role in cell immunity and phagocytosis, processes that require rearrangement of the cytoskeleton. However, the detailed mechanism by which miR-146a regulates these events remains elusive. Here, we used luciferase reporter and protein assays to show that the cytoskeleton-regulatingprotein verprolin-homologous protein 2 (WAVE2), is a direct target of miR-146a. MiR-146a overexpression resulted in a decrease in WAVE2 protein expression under endotoxin-free ...[more]

PMID: 26396677

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Project description:Recent studies confirm that chronic low-grade inflammation is closely associated with metabolic syndromes, and anti-inflammatory therapy is a potential approach for treating cardiovascular diseases and type 2 diabetes. Accumulating evidence suggests that GPR120 activation is a feasible solution to ameliorating chronic inflammation and improving glucose metabolism. In this study we investigated whether ginsenoside Rb2 (Rb2), which exhibited regulatory activities in glucose and lipid metabolism, affected GPR120 expression in lipopolysaccharide (LPS)-activated mouse macrophage RAW264.7 cells, and examined the contribution of GPR120 activation to reducing the LPS-induced inflammatory response. LPS (100 ng/mL) activated the macrophages, resulting in dramatic increases in TNF-α, IL-6, IL-1β and NO production. Treatment with a ω-3 fatty acid α-linolenic acid (ALA, 50 μmol/L) produced moderate reduction in LPS-stimulated inflammatory cytokines and NO production (TNF-α and IL-6 were decreased by 46% and 42%, respectively). Pre-incubation with Rb2 (1 or 10 μmol/L) for 12 h before ALA treatment dramatically amplified the inhibitory effects of ALA (TNF-α and IL-6 were decreased by 74% and 86%, respectively). Compared to the treatment with ALA alone, pre-incubation with Rb2 resulted in a more prominent reduction in LPS-stimulated expression of iNOS and COX-2 and LPS-stimulated IKK/NF-κB phosphorylation and MAPK pathway activation. Rb2 (0.1-100 μmol/L) dose- and time-dependently increased both mRNA and protein expression of GPR120 in RAW264.7 cells, but treatment with Rb2 alone did not exert anti-inflammatory effect in LPS-activated RAW264.7 cells. In RAW264.7 cells transfected with GPR120 shRNA, the ameliorating effects of Rb2 on LPS-induced inflammation were abolished. In conclusion, Rb2 exerts anti-inflammatory effect in LPS-stimulated mouse macrophage RAW264.7 cells in vitro by increasing GPR120 expression and subsequently enhancing ω-3 fatty acid-induced GPR120 activation.

Dataset Information

MiR-146a activates WAVE2 expression and enhances phagocytosis in lipopolysaccharide-stimulated RAW264.7 macrophages.

Publications

MiR-146a activates WAVE2 expression and enhances phagocytosis in lipopolysaccharide-stimulated RAW264.7 macrophages.

Similar Datasets

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