Internalization of Staphylococcus aureus by bovine endothelial cells is associated with the activity state of NF-κB and modulated by the pro-inflammatory cytokines TNF-α and IL-1β

Abstract

Bacterial internalization is an important process in the pathogenesis of infectious diseases in which nuclear factor kappaB (NF-κB) plays a prominent role. We present pharmacological evidence indicating that in bovine endothelial cells (BEC) the internalization of Staphylococcus aureus, a pathogenic bacterium that causes mastitis in bovine cattle, was associated with the activation of NF-κB. The internalization of S. aureus increased when BEC were stimulated with alpha-tumour necrosis factor (TNF-α) or beta-interleukin 1 (IL-1β) which are known activators of NF-κB. SN50 (an inhibitor peptide of NF-κB nuclear translocation) and BAY 11-7083 (a chemical that inhibits the IκBα phosphorylation) caused significant reduction in S. aureus intracellular number, indicating that its internalization was associated with the NF-κB activity. Furthermore, specific inhibition of c-Jun N-terminal kinase with SP600125 (SP) or p-38 with SB203580 (SB) did not cause any change in the S. aureus intracellular number compared with the untreated control. Finally, TNF-α treatment of BEC after the addition of both SP and SB, induced a significant increase in S. aureus internalization above the control value. These data indicate that NF-κB activity is associated with S. aureus internalization and suggest that this transcription factor may play a role in the pathophysiology of bovine mastitis caused by this bacterium. © 2008 The Authors.