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Inflammation
Dec, 2019;42 (6): 2192-2204.

6-Bromoindirubin-3'-Oxime Suppresses LPS-Induced Inflammation via Inhibition of the TLR4/NF-κB and TLR4/MAPK Signaling Pathways.

Chang Liu, Xin Tang, Wenjing Zhang, Guohong Li, Yingyu Chen, Aizhen Guo, Changmin Hu
Author Information
  1. Chang Liu: The Faculty of Veterinary Medicine, Huazhong Agricultural University, Wuhan, 430070, China.
  2. Xin Tang: The Faculty of Veterinary Medicine, Huazhong Agricultural University, Wuhan, 430070, China.
  3. Wenjing Zhang: The Faculty of Veterinary Medicine, Huazhong Agricultural University, Wuhan, 430070, China.
  4. Guohong Li: The Faculty of Veterinary Medicine, Huazhong Agricultural University, Wuhan, 430070, China.
  5. Yingyu Chen: The Faculty of Veterinary Medicine, Huazhong Agricultural University, Wuhan, 430070, China.
  6. Aizhen Guo: The Faculty of Veterinary Medicine, Huazhong Agricultural University, Wuhan, 430070, China.
  7. Changmin Hu: The Faculty of Veterinary Medicine, Huazhong Agricultural University, Wuhan, 430070, China. hcm@mail.hzau.edu.cn.
PMID: 31599382 DOI: 10.1007/s10753-019-01083-1

Abstract

We investigated the efficacy of the traditional herbal extract 6-bromoindirubin-3'-oxime (BIO) against lipopolysaccharide (LPS)-induced mastitis in mice and inflammatory signaling in mouse mammary epithelial cells (MMECs). In vivo, breast inflammation scores and enzyme-linked immunosorbent assay (ELISA) detection of pro-inflammatory factor expression were used to assess the effect of BIO against mastitis. In vitro, the effects of BIO on LPS-induced changes in the expression levels of pro-inflammatory factors, anti-inflammatory cytokines, and signaling factors of the toll-like receptor 4 (TLR4)/nuclear factor-κB (NF-κB) and TLR4/mitogen-activated protein kinase (MAPK) pathways were examined by qRT-PCR and ELISA. In LPS-injected mice, BIO pretreatment downregulated the expression of the pro-inflammatory factors interleukin (IL)-1β, IL-6, tumor necrosis factor (TNF)-α, and myeloperoxidase (MPO) in mammary glands and reduced inflammatory lesions in breast tissue. In MMECs, BIO pretreatment downregulated the LPS-induced expression of IL-1β, IL-6, and TNF-α. Further, BIO inhibited both the expression and phosphorylation of TLR4/NF-κB and TLR4/MAPK signaling factors. Thus, BIO downregulates IL-6, IL-1β, TNF-α, and MPO expression, upregulates IL-10 expression, and suppresses LPS-induced inflammation by inhibiting the TLR4/NF-κB and TLR4/MAPK pathways. BIO may be a potential treatment agent for mastitis and other inflammatory diseases.

Keywords

BIO MAPK NF-κB TLR4 inflammation lipopolysaccharide (LPS)

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Grants

  1. No. CARS-38/China Agriculture Research System (Beef/Yak cattle)
  2. No. 2016YFD0500906/National Key Research and Development Plan

MeSH Term

Animals
Female
Indoles
Inflammation
Lipopolysaccharides
MAP Kinase Signaling System
Mammary Glands, Animal
Mastitis
Mice
NF-kappa B
Oximes
Signal Transduction
Toll-Like Receptor 4

Chemicals

6-bromoindirubin-3'-oxime
Indoles
Lipopolysaccharides
NF-kappa B
Oximes
Tlr4 protein, mouse
Toll-Like Receptor 4
Journal Article

Word Cloud

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