title: Indirubin Treatment of Lipopolysaccharide-Induced Mastitis in a Mouse Model and Activity in Mouse Mammary Epithelial Cells.
abstract: 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.
authors.affiliation: The Faculty of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, China.
authors.forename: Jin-Lun
authors.initials: JL
authors.lastname: Lai
authors.affiliation: The Faculty of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, China.
authors.forename: Yu-Hui
authors.initials: YH
authors.lastname: Liu
authors.affiliation: The Faculty of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, China.
authors.forename: Yong-Chong
authors.initials: YC
authors.lastname: Peng
authors.affiliation: The Faculty of Animal Sciences and Technology, Huazhong Agricultural University, Wuhan 430070, China.
authors.forename: Pan
authors.initials: P
authors.lastname: Ge
authors.affiliation: The Faculty of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, China.
authors.forename: Chen-Fei
authors.initials: CF
authors.lastname: He
authors.affiliation: The Faculty of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, China.
authors.forename: Chang
authors.initials: C
authors.lastname: Liu
authors.affiliation: The Faculty of Animal Sciences and Technology, Huazhong Agricultural University, Wuhan 430070, China; State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan 430070, China.
authors.forename: Ying-Yu
authors.initials: YY
authors.lastname: Chen
authors.affiliation: The Faculty of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, China; State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan 430070, China.
authors.forename: Ai-Zhen
authors.initials: AZ
authors.lastname: Guo
authors.affiliation: The Faculty of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, China; State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan 430070, China.
authors.forename: Chang-Min
authors.identifier: 0000-0003-2279-0851
authors.initials: CM
authors.lastname: Hu
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D015153:Blotting, Western; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000378:metabolism; D006801:Humans; D007211:Indoles / Q000627:therapeutic use; D053583:Interleukin-1beta / Q000378:metabolism; D007377:Interleukin-3 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008070:Lipopolysaccharides / Q000633:toxicity*; D008297:Male; D042361:Mammary Glands, Human / Q000166:cytology / Q000378:metabolism* / Q000473:pathology; D008413:Mastitis / Q000139:chemically induced* / Q000188:drug therapy* / Q000378:metabolism; D051379:Mice; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D007211:Indoles; D053583:Interleukin-1beta; D007377:Interleukin-3; D015850:Interleukin-6; D008070:Lipopolysaccharides; D011993:Recombinant Fusion Proteins; D014409:Tumor Necrosis Factor-alpha; C404145:myelopoietin; D016179:Granulocyte Colony-Stimulating Factor; C027185:indirubin