The role of Ca(2+) mediated signaling pathways on the effect of taurine against Streptococcus uberis infection

Vet Microbiol. 2016 Aug 30;192:26-33. doi: 10.1016/j.vetmic.2016.06.008. Epub 2016 Jun 21.


To provide insight into the mechanisms of taurine attenuation of pro-inflammatory response in mouse mammary epithelial cell line (EpH4-Ev, purchased by ATCC, USA) after Streptococcus uberis (S. uberis, 0140J) challenge, we infected MECs with S. uberis (2.5×10(7)cfumL(-1), MOI=10) for 3h and quantified changes in TLR-2 and calcium (Ca(2+)) mediated signaling pathways. The results indicate that S. uberis infection significantly increases the expression of TLR-2, intracellular Ca(2+) levels, PLC-γ1 and PKC-α, the activities of transcription factors NF-κB and NFAT, and related cytokines (TNF-α, IL-1β, IL-6, G-CSF, IL-2, KC, IL-15, FasL, MCP-1, and LIX) in culture supernatants. Taurine administration downregulated all these indices, the activities of NF-κB and NFAT. Cytokine secretions were similar using special PKC inhibitor Go 6983 and NFAT inhibitor VIVIT. Our data indicate that S. uberis infection induces pro-inflammatory response of MECs through a TLR-2 mediated signaling pathway. In addition, taurine can prevent MEC damage by affecting both PLC-γ1-Ca(2+)-PKC-α-NF-κB and PLC-γ1-Ca(2+)-NFATs signaling pathways. This is the first report to demonstrate the mechanisms of taurine attenuated pro-inflammatory response in MECs after S. uberis challenge.

Keywords: Ca(2+); Mouse mammary epithelial cell; Streptococcus uberis; Taurine.

MeSH terms

  • Animals
  • Calcium / metabolism*
  • Cell Line
  • Cytokines
  • Epithelial Cells / microbiology*
  • Female
  • Gene Expression Regulation / drug effects
  • Mammary Glands, Animal / cytology*
  • Mice
  • NF-kappa B / genetics
  • NF-kappa B / metabolism
  • NFATC Transcription Factors / genetics
  • NFATC Transcription Factors / metabolism
  • Phospholipase C gamma / genetics
  • Phospholipase C gamma / metabolism
  • Protein Kinase C-alpha / genetics
  • Protein Kinase C-alpha / metabolism
  • Signal Transduction / drug effects*
  • Signal Transduction / physiology
  • Streptococcus / classification*
  • Streptococcus / isolation & purification
  • Taurine / pharmacology*
  • Toll-Like Receptor 2 / genetics
  • Toll-Like Receptor 2 / metabolism


  • Cytokines
  • NF-kappa B
  • NFATC Transcription Factors
  • Nfatc1 protein, mouse
  • Tlr2 protein, mouse
  • Toll-Like Receptor 2
  • Taurine
  • Protein Kinase C-alpha
  • Phospholipase C gamma
  • Calcium