TRAM-Derived Decoy Peptides inhibits the inflammatory response in mouse mammary epithelial cells and a mastitis model in mice

Eur J Pharmacol. 2015 Oct 5:764:607-612. doi: 10.1016/j.ejphar.2015.06.022. Epub 2015 Jun 19.

Abstract

It has been proved that TRAM-Derived Decoy peptides have anti-inflammatory properties. In this study, we synthesized a TRAM-Derived decoy peptide (TM6), belongs to TRAM TIR domain, of which sequence is "N"-RQIKIWFQNRRMKWK, KENFLRDTWCNFQFY-"C" and evaluated the effects of TM6 on lipopolysaccharide-induced mastitis in mice. In vivo, LPS-induced mice mastitis model was established by injection of LPS through the duct of mammary gland. TM6 was injected 1h before or after LPS treatment. In vitro, primary mouse mammary epithelial cells were used to investigate the effects of TM6 on LPS-induced inflammatory responses. The results showed that TM6 inhibited LPS-induced mammary gland histopathologic changes, MPO activity, and TNF-α, IL-1β and IL-6 production in mice. In vitro, TM6 significantly inhibited LPS-induced TNF-α and IL-6 production, as well as NF-κB and MAPKs activation. In conclusion, this study demonstrated that TM6 had protective effects on LPS-mastitis and may be a promising therapeutic reagent for mastitis treatment.

Keywords: Cytokines; LPS; Mastitis; TLR4; TRAM-Derived Decoy Peptide.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / pharmacology*
  • Animals
  • Anti-Inflammatory Agents / pharmacology*
  • Cytokines / metabolism
  • Disease Models, Animal
  • Epithelial Cells / drug effects*
  • Epithelial Cells / immunology
  • Epithelial Cells / metabolism
  • Female
  • Inflammation Mediators / metabolism*
  • Lipopolysaccharides
  • Male
  • Mammary Glands, Animal / drug effects*
  • Mammary Glands, Animal / immunology
  • Mammary Glands, Animal / metabolism
  • Mastitis / chemically induced
  • Mastitis / drug therapy*
  • Mastitis / immunology
  • Mastitis / metabolism
  • Mice, Inbred BALB C
  • Mitogen-Activated Protein Kinases / metabolism
  • NF-kappa B / metabolism
  • Peptide Fragments / pharmacology*
  • Peroxidase / metabolism
  • Time Factors
  • Tissue Culture Techniques

Substances

  • Adaptor Proteins, Signal Transducing
  • Anti-Inflammatory Agents
  • Cytokines
  • Inflammation Mediators
  • Lipopolysaccharides
  • NF-kappa B
  • Peptide Fragments
  • Peroxidase
  • Mitogen-Activated Protein Kinases