Indirubin Inhibits LPS-Induced Inflammation via TLR4 Abrogation Mediated by the NF-kB and MAPK Signaling Pathways

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• 作者：Jin-lun Lai ; Yu-hui Liu ; Chang Liu ; Ming-pu Qi ; Rui-ning Liu ; Xi-fang Zhu&#8230
• 关键词：KEY WORDSindirubin ; lipopolysaccharide (LPS) ; TLR4 ; NF ; kB ; MAPK ; inflammation
• 刊名：Inflammation
• 出版年：2017
• 出版时间：February 2017
• 年：2017
• 卷：40
• 期：1
• 页码：1-12
• 全文大小：
• 刊物类别：Medicine
• 刊物主题：Rheumatology; Internal Medicine; Pharmacology/Toxicology; Pathology;
• 出版者：Springer US
• ISSN：1573-2576
• 卷排序：40

文摘

Indirubin plays an important role in the treatment of many chronic diseases and exhibits strong anti-inflammatory activity. However, the molecular mode of action during mastitis prophylaxis remains poorly understood. In this study, a lipopolysaccharide (LPS)-induced mastitis mouse model showed that indirubin attenuated histopathological changes in the mammary gland, local tissue necrosis, and neutrophil infiltration. Moreover, indirubin significantly downregulated the production of interleukin (IL)-1β, IL-6, and tumor necrosis factor-α (TNF-α). We explored the mechanism whereby indirubin exerts protective effects against LPS-induced inflammation of mouse mammary epithelial cells (MMECs). The addition of different concentrations of indirubin before exposure of cells to LPS for 1 h significantly attenuated inflammation and reduced the concentrations of the three inflammatory cytokines in a dose-dependent manner. Indirubin downregulated LPS-induced cyclooxygenase-2 (COX-2) and Toll-like receptor 4 (TLR4) expression, inhibited phosphorylation of the LPS-induced nuclear transcription factor-kappa B (NF-kB) P65 protein and its inhibitor IkBα of the NF-kB signaling pathway. Furthermore, indirubin suppressed phosphorylation of P38, extracellular signal-regulated kinase (ERK), and c-Jun NH₂-terminal kinase (JNK) of the mitogen-activated protein kinase (MAPK) signal pathways. Thus, indirubin effectively suppressed LPS-induced inflammation via TLR4 abrogation mediated by the NF-kB and MAPK signaling pathways and may be useful for mastitis prophylaxis.