Staphylococcus aureus induces apoptosis in primary bovine mammary epithelial cells through Fas-FADD death receptor-linked caspase-8 signaling

DNA Cell Biol. 2014 Jun;33(6):388-97. doi: 10.1089/dna.2013.2195. Epub 2014 Feb 24.

Abstract

Infections with Staphylococcus aureus, a common inducer of mastitis, often result in mammary gland damage and death of various cell types. Although S. aureus was suggested to induce apoptosis in a bovine mammary epithelial cell (BMEC) line, MAC-T, it is unknown whether primary BMECs (pBMECs) apoptosis is triggered by S. aureus and the associated underlying molecular mechanisms have not been determined. Here, we demonstrated that S. aureus induced apoptosis in pBMECs in a time- and dose-dependent manner. Further, S. aureus-induced apoptosis in pBMECs was associated with activation of caspase-3 and caspase-8, but caspase-9 was not. In addition, pBMECs apoptosis was mitigated by caspase-3 and caspase-8 inhibitors, suggesting that apoptosis is initiated via caspase-8 activation. Moreover, S. aureus infection significantly increased expressions of Fas and Fas-associated death domain (FADD) of pBMECs. Taken together, our results demonstrated that S. aureus induced apoptosis in pBMECs via the Fas-FADD death receptor and subsequently triggered the caspase-8-dependent signaling.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis* / drug effects
  • Caspase 3
  • Caspase 8 / metabolism*
  • Caspase Inhibitors / pharmacology
  • Cattle
  • Cell Line
  • Epithelial Cells / metabolism*
  • Fas-Associated Death Domain Protein / metabolism
  • Female
  • Mammary Glands, Animal / pathology*
  • Mastitis, Bovine / pathology*
  • Signal Transduction*
  • Staphylococcal Infections / pathology
  • Staphylococcal Infections / veterinary*
  • Staphylococcus aureus
  • fas Receptor / metabolism

Substances

  • Caspase Inhibitors
  • Fas-Associated Death Domain Protein
  • fas Receptor
  • Caspase 3
  • Caspase 8