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

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Abstract

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.

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Acknowledgments

We are grateful for the financial support from the National Key Basic Research Program of China (2012CB518404), the National Natural Science Foundation of China (81273891), the National Science Fund for Distinguished Young Scholars (81125024), and the Program for Changjiang Scholars and Innovative Research Team in University (IRT1276).

Conflict of Interest

The authors declare no competing financial interest.

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Authors and Affiliations

  1. State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, #312 Anshanxi Road, Nankai District, Tianjin, 300193, China

    Guanwei Fan, Xiaorui Jiang, Xiaoyan Wu, Patrick Asare Fordjour, Lin Miao, Han Zhang, Yan Zhu & Xiumei Gao

  2. Ministry of Education Key Laboratory of Pharmacology of Traditional Chinese Medical Formulae, Tianjin University of Traditional Chinese Medicine, Tianjin, 300193, China

    Guanwei Fan, Xiaorui Jiang, Xiaoyan Wu, Patrick Asare Fordjour, Lin Miao, Han Zhang, Yan Zhu & Xiumei Gao

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  1. Guanwei Fan
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  2. Xiaorui Jiang
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Correspondence to Xiumei Gao.

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Fan, G., Jiang, X., Wu, X. et al. Anti-Inflammatory Activity of Tanshinone IIA in LPS-Stimulated RAW264.7 Macrophages via miRNAs and TLR4–NF-κB Pathway. Inflammation 39, 375–384 (2016). https://doi.org/10.1007/s10753-015-0259-1

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