Nisin Z attenuates lipopolysaccharide-induced mastitis by inhibiting the ERK1/2 and p38 mitogen-activated protein kinase signaling pathways

J Dairy Sci. 2022 Apr;105(4):3530-3543. doi: 10.3168/jds.2021-21356. Epub 2022 Feb 16.

Abstract

Nisin Z is a possible alternative for treating bovine mastitis by inhibiting mastitis-causing pathogens and having anti-inflammatory activity. However, the anti-inflammatory mechanism of nisin Z on mastitis is unknown. Our study aimed to investigate the mechanisms of nisin Z on mastitis. Our results showed that nisin Z inhibited the activation of the ERK1/2 and p38 mitogen-activated protein kinase (MAPK) signaling pathway, decreased the release of pro-inflammatory cytokines (i.e., tumor necrosis factor-α, IL-1β, and IL-6), and increased the anti-inflammatory cytokine (IL-10) in lipopolysaccharide (LPS)-induced MCF10A cells. After intraperitoneal injection, nisin Z significantly decreased inflammatory cell infiltration in the mammary gland, as well as decreased myeloperoxidase and pro-inflammatory cytokines in serum and mammary gland. Western blot analysis revealed that nisin Z also dramatically suppressed the activation of the ERK1/2 and p38 MAPK signaling pathways in LPS-induced mastitis mice. We also found that nisin Z treatment could enhance the blood-milk barrier. In summary, our study demonstrated that nisin Z exerted an anti-inflammatory effect by inhibiting the ERK1/2 and p38 MAPK signaling pathway and promoting the blood-milk barrier on LPS-induced mastitis.

Keywords: blood-milk barrier; mastitis; mitogen-activated protein kinase; nisin Z.

MeSH terms

  • Animals
  • Cattle
  • Cattle Diseases*
  • Female
  • Lipopolysaccharides / pharmacology
  • MAP Kinase Signaling System
  • Mastitis* / chemically induced
  • Mastitis* / drug therapy
  • Mastitis* / veterinary
  • Mice
  • NF-kappa B / metabolism
  • Nisin / analogs & derivatives
  • Signal Transduction
  • p38 Mitogen-Activated Protein Kinases / metabolism

Substances

  • Lipopolysaccharides
  • NF-kappa B
  • Nisin
  • p38 Mitogen-Activated Protein Kinases
  • nisin Z