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Indirubin Treatment of Lipopolysaccharide-Induced Mastitis in a Mouse Model and Activity in Mouse Mammary Epithelial Cells

Indirubin is a Chinese medicine extracted from indigo and known to be effective for treating chronic myelogenous leukemia, neoplasia, and inflammatory disease. This study evaluated the in vivo anti-inflammatory activity of indirubin in a lipopolysaccharide- (LPS-) induced mouse mastitis model. The i...

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Autores principales: Lai, Jin-lun, Liu, Yu-hui, Peng, Yong-chong, Ge, Pan, He, Chen-fei, Liu, Chang, Chen, Ying-yu, Guo, Ai-zhen, Hu, Chang-min
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi Publishing Corporation 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5309412/
https://www.ncbi.nlm.nih.gov/pubmed/28255203
http://dx.doi.org/10.1155/2017/3082805
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author Lai, Jin-lun
Liu, Yu-hui
Peng, Yong-chong
Ge, Pan
He, Chen-fei
Liu, Chang
Chen, Ying-yu
Guo, Ai-zhen
Hu, Chang-min
author_facet Lai, Jin-lun
Liu, Yu-hui
Peng, Yong-chong
Ge, Pan
He, Chen-fei
Liu, Chang
Chen, Ying-yu
Guo, Ai-zhen
Hu, Chang-min
author_sort Lai, Jin-lun
collection PubMed
description Indirubin is a Chinese medicine extracted from indigo and known to be effective for treating chronic myelogenous leukemia, neoplasia, and inflammatory disease. This study evaluated the in vivo anti-inflammatory activity of indirubin in a lipopolysaccharide- (LPS-) induced mouse mastitis model. The indirubin mechanism and targets were evaluated in vitro in mouse mammary epithelial cells. In the mouse model, indirubin significantly attenuated the severity of inflammatory lesions, edema, inflammatory hyperemia, milk stasis and local tissue necrosis, and neutrophil infiltration. Indirubin significantly decreased myeloperoxidase activity and downregulated the production of tumor necrosis factor-α, interleukin-1β (IL-1β), and IL-6 caused by LPS. In vitro, indirubin inhibited LPS-stimulated expression of proinflammatory cytokines in a dose-dependent manner. It also downregulated LPS-induced toll-like receptor 4 (TLR4) expression and inhibited phosphorylation of LPS-induced nuclear transcription factor-kappa B (NF-κB) P65 protein and inhibitor of kappa B. In addition to its effect on the NF-κB signaling pathway, indirubin suppressed the mitogen-activated protein kinase (MAPK) signaling by inhibiting phosphorylation of extracellular signal-regulated kinase (ERK), P38, and c-jun NH2-terminal kinase (JNK). Indirubin improved LPS-induced mouse mastitis by suppressing TLR4 and downstream NF-κB and MAPK pathway inflammatory signals and might be a potential treatment of mastitis and other inflammatory diseases.
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spelling pubmed-53094122017-03-02 Indirubin Treatment of Lipopolysaccharide-Induced Mastitis in a Mouse Model and Activity in Mouse Mammary Epithelial Cells Lai, Jin-lun Liu, Yu-hui Peng, Yong-chong Ge, Pan He, Chen-fei Liu, Chang Chen, Ying-yu Guo, Ai-zhen Hu, Chang-min Mediators Inflamm Research Article Indirubin is a Chinese medicine extracted from indigo and known to be effective for treating chronic myelogenous leukemia, neoplasia, and inflammatory disease. This study evaluated the in vivo anti-inflammatory activity of indirubin in a lipopolysaccharide- (LPS-) induced mouse mastitis model. The indirubin mechanism and targets were evaluated in vitro in mouse mammary epithelial cells. In the mouse model, indirubin significantly attenuated the severity of inflammatory lesions, edema, inflammatory hyperemia, milk stasis and local tissue necrosis, and neutrophil infiltration. Indirubin significantly decreased myeloperoxidase activity and downregulated the production of tumor necrosis factor-α, interleukin-1β (IL-1β), and IL-6 caused by LPS. In vitro, indirubin inhibited LPS-stimulated expression of proinflammatory cytokines in a dose-dependent manner. It also downregulated LPS-induced toll-like receptor 4 (TLR4) expression and inhibited phosphorylation of LPS-induced nuclear transcription factor-kappa B (NF-κB) P65 protein and inhibitor of kappa B. In addition to its effect on the NF-κB signaling pathway, indirubin suppressed the mitogen-activated protein kinase (MAPK) signaling by inhibiting phosphorylation of extracellular signal-regulated kinase (ERK), P38, and c-jun NH2-terminal kinase (JNK). Indirubin improved LPS-induced mouse mastitis by suppressing TLR4 and downstream NF-κB and MAPK pathway inflammatory signals and might be a potential treatment of mastitis and other inflammatory diseases. Hindawi Publishing Corporation 2017 2017-02-01 /pmc/articles/PMC5309412/ /pubmed/28255203 http://dx.doi.org/10.1155/2017/3082805 Text en Copyright © 2017 Jin-lun Lai et al. https://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Lai, Jin-lun
Liu, Yu-hui
Peng, Yong-chong
Ge, Pan
He, Chen-fei
Liu, Chang
Chen, Ying-yu
Guo, Ai-zhen
Hu, Chang-min
Indirubin Treatment of Lipopolysaccharide-Induced Mastitis in a Mouse Model and Activity in Mouse Mammary Epithelial Cells
title Indirubin Treatment of Lipopolysaccharide-Induced Mastitis in a Mouse Model and Activity in Mouse Mammary Epithelial Cells
title_full Indirubin Treatment of Lipopolysaccharide-Induced Mastitis in a Mouse Model and Activity in Mouse Mammary Epithelial Cells
title_fullStr Indirubin Treatment of Lipopolysaccharide-Induced Mastitis in a Mouse Model and Activity in Mouse Mammary Epithelial Cells
title_full_unstemmed Indirubin Treatment of Lipopolysaccharide-Induced Mastitis in a Mouse Model and Activity in Mouse Mammary Epithelial Cells
title_short Indirubin Treatment of Lipopolysaccharide-Induced Mastitis in a Mouse Model and Activity in Mouse Mammary Epithelial Cells
title_sort indirubin treatment of lipopolysaccharide-induced mastitis in a mouse model and activity in mouse mammary epithelial cells
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5309412/
https://www.ncbi.nlm.nih.gov/pubmed/28255203
http://dx.doi.org/10.1155/2017/3082805
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