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

• DOI: 10.1007/s10753-015-0259-1
• Publication Date: 2015-12-06T21:58:21Z
• Authors: Guanwei Fan; Xiaorui Jiang; Xiaoyan Wu; Patrick Asare For...; Lin Miao; Han Zhang; Yan Zhu; Xiumei Gao
• Keywords: Inflammation; Lipopolysaccharides; 0303 health sciences; Macrophages; Anti-Inflammatory Agents; NF-kappa B; Gene Expression; Cell Line; 3. Good health; Toll-Like Receptor 4; Mice; MicroRNAs; 03 medical and health sciences; Abietanes; Myeloid Differentiation Factor 88; Animals; Cytokines; Humans; Drugs, Chinese Herbal; HeLa Cells; Signal Transduction

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.