title: Anti-Inflammatory Activity of Tanshinone IIA in LPS-Stimulated RAW264.7 Macrophages via miRNAs and TLR4-NF-κB Pathway.
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.
authors.affiliation: State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, #312 Anshanxi Road, Nankai District, Tianjin, 300193, China.|Ministry of Education Key Laboratory of Pharmacology of Traditional Chinese Medical Formulae, Tianjin University of Traditional Chinese Medicine, Tianjin, 300193, China.
authors.forename: Guanwei
authors.initials: G
authors.lastname: Fan
authors.affiliation: State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, #312 Anshanxi Road, Nankai District, Tianjin, 300193, China.|Ministry of Education Key Laboratory of Pharmacology of Traditional Chinese Medical Formulae, Tianjin University of Traditional Chinese Medicine, Tianjin, 300193, China.
authors.forename: Xiaorui
authors.initials: X
authors.lastname: Jiang
authors.affiliation: State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, #312 Anshanxi Road, Nankai District, Tianjin, 300193, China.|Ministry of Education Key Laboratory of Pharmacology of Traditional Chinese Medical Formulae, Tianjin University of Traditional Chinese Medicine, Tianjin, 300193, China.
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Wu
authors.affiliation: State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, #312 Anshanxi Road, Nankai District, Tianjin, 300193, China.|Ministry of Education Key Laboratory of Pharmacology of Traditional Chinese Medical Formulae, Tianjin University of Traditional Chinese Medicine, Tianjin, 300193, China.
authors.forename: Patrick Asare
authors.initials: PA
authors.lastname: Fordjour
authors.affiliation: State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, #312 Anshanxi Road, Nankai District, Tianjin, 300193, China.|Ministry of Education Key Laboratory of Pharmacology of Traditional Chinese Medical Formulae, Tianjin University of Traditional Chinese Medicine, Tianjin, 300193, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Miao
authors.affiliation: State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, #312 Anshanxi Road, Nankai District, Tianjin, 300193, China.|Ministry of Education Key Laboratory of Pharmacology of Traditional Chinese Medical Formulae, Tianjin University of Traditional Chinese Medicine, Tianjin, 300193, China.
authors.forename: Han
authors.initials: H
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, #312 Anshanxi Road, Nankai District, Tianjin, 300193, China.|Ministry of Education Key Laboratory of Pharmacology of Traditional Chinese Medical Formulae, Tianjin University of Traditional Chinese Medicine, Tianjin, 300193, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, #312 Anshanxi Road, Nankai District, Tianjin, 300193, China. gaoxiumei@tjutcm.edu.cn.|Ministry of Education Key Laboratory of Pharmacology of Traditional Chinese Medical Formulae, Tianjin University of Traditional Chinese Medicine, Tianjin, 300193, China. gaoxiumei@tjutcm.edu.cn.
authors.forename: Xiumei
authors.initials: X
authors.lastname: Gao
mesh_terms: D045784:Abietanes / Q000494:pharmacology*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D002460:Cell Line; D016207:Cytokines / Q000096:biosynthesis*; D004365:Drugs, Chinese Herbal / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects; D006367:HeLa Cells; D006801:Humans; D007249:Inflammation / Q000188:drug therapy; D008070:Lipopolysaccharides; D008264:Macrophages / Q000276:immunology*; D051379:Mice; D035683:MicroRNAs / Q000096:biosynthesis* / Q000235:genetics; D053594:Myeloid Differentiation Factor 88 / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D051197:Toll-Like Receptor 4 / Q000378:metabolism*
chemical_list: D045784:Abietanes; D000893:Anti-Inflammatory Agents; D016207:Cytokines; D004365:Drugs, Chinese Herbal; D008070:Lipopolysaccharides; D035683:MicroRNAs; C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88; D016328:NF-kappa B; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4; C021751:tanshinone
keywords: TLR4–NF-κB pathway; inflammatory mediators; microRNA; tanshinone IIA