Anti-Inflammatory Activity of Tanshinone IIA in LPS-Stimulated RAW264.7 Macrophages via miRNAs and TLR4–NF-κB Pathway

📖 Top 20% JournalDec 8, 2015Inflammation

Tanshinone IIA reduces inflammation in immune cells by affecting gene regulators and the TLR4-NF-κB signaling pathway

AI simplified

Abstract

Tanshinone IIA could reduce cytokine production, including tumor necrosis factor alpha (TNF-α), in LPS-induced RAW264.7 cells.

Tan IIA may inhibit the inflammatory response by decreasing levels of several inflammatory markers.
Significant reductions in messenger RNA (mRNA) expressions of IL-1β, TNF-α, and COX-2 were noted with Tan IIA treatment.
Tan IIA could diminish the activation of a specific signaling pathway (TLR4-MyD88-NF-κB) associated with inflammation.
Expression levels of various microRNAs were altered by Tan IIA, indicating potential regulatory effects on gene expression.
LPS treatment was associated with increased expression of certain microRNAs, which were decreased by Tan IIA.

AI simplified

Inflammation is a physiological response to infection or injury and involves the innate and adaptive immune system. Tanshinone IIA (Tan IIA) is a well-known flavonoid that elicits an important therapeutic effect by inhibiting inflammatory response. In this study, we examined whether Tan IIA exerts anti-inflammatory activity and investigated the possible mechanisms, including Toll-like receptor 4 (TLR4)-MyD88-nuclear factor kappa B (NF-κB) signaling pathway and microRNA expression in lipopolysaccharide (LPS)-induced RAW264.7 cells. Tan IIA could attenuate the inflammatory reaction via decreasing cytokine, chemokine, and acute-phase protein production, including GM-CSF, sICAM-1, cxcl-1, MIP-1α, and tumor necrosis factor alpha (TNF-α), analyzed by Proteome profile array in LPS-induced RAW264.7 cells. Concurrently, the messenger RNA (mRNA) expressions of IL-1β, TNF-α, and COX-2 were also significantly reduced by Tan IIA. Additionally, Tan IIA decreased LPS-induced NF-κB activation and downregulated TLR4 and MyD88 protein expression levels. We also observed reduced microRNA-155, miR-147, miR-184, miR-29b, and miR-34c expression levels, while LPS-induced microRNA-105, miR-145a, miR-194, miR-383, miR-132, and miR-451a expression levels were upregulated using microRNA (miRNA) qPCR array. Our results indicate that Tan IIA could exert an anti-inflammatory effect on LPS-induced RAW264.7 cells by decreasing TLR4-MyD88-NF-κB signaling pathway and regulating a series of cytokine production and miRNA expression.

Full Text

Full text is available at the source.

View full text (PDF) ↗View full text (HTML) ↗View full text ↗