title: Staphylococcus aureus regulates secretion of interleukin-6 and monocyte chemoattractant protein-1 through activation of nuclear factor kappaB signaling pathway in human osteoblasts.
abstract: OBJECTIVE
  Activation of nuclear factor kappaB by diverse bacteria regulates the secretion of chemokines and cytokines. Staphylococcus aureus (S. aureus)-infected osteoblasts can significantly increase the secretion of interleukin-6 and monocyte chemoattractant protein-1. The aim of this study was to investigate whether S. aureus can activate nuclear factor kappaB in human osteoblasts, and whether the activation of nuclear factor kappaB by S. aureus regulates the secretion of interleukin-6 and monocyte chemoattractant protein-1.
  
  
  METHODS
  Immunoblot and electrophoretic mobility shift assay were used to detect the degradation of IκBa and activation of nuclear factor kappaB in human osteoblasts in response to S. aureus, respectively. Enzyme-linked immunosorbent assay was used to measure the secretion of interleukin-6 and monocyte chemoattractant protein-1 in the supernatants. Lastly, carbobenzoxyl-l-leucinyl-l-leucinyl-l-leucinal, an inhibitor of the nuclear factor kappaB, was used to determine if activation of nuclear factor kappaB by S. aureus in human osteoblasts regulates the secretions of interleukin-6 and monocyte chemoattractant protein-1.
  
  
  RESULTS
  Our results for the first time demonstrated that S. aureus can induce the degradation of IκBa and activation of nuclear factor kappaB in human osteoblasts in a time and dose-dependent manner. In addition, inhibition of nuclear factor kappaB by carbobenzoxyl-l-leucinyl-l-leucinyl-l-leucinal suppressed the secretion of interleukin-6 and monocyte chemoattractant protein-1 in the supernatants of S. aureus-infected human osteoblasts in a dose-dependent manner.
  
  
  CONCLUSIONS
  These findings suggest that S. aureus can activate nuclear factor kappaB in human osteoblasts, and subsequently regulate the secretion of interleukin-6 and monocyte chemoattractant protein-1. The nuclear factor kappaB transcription factor regulates a number of genes involved in a wide variety of biological processes. Further study of the effects of nuclear factor kappaB activation on S. aureus-infected human osteoblast may provide us new insights into discovery of the immune mechanisms in osteomyelitis.
authors.affiliation: Department of Orthopaedics, The Sixth People's Hospital Affiliated, Shanghai Jiao Tong University, China.
authors.forename: Rende
authors.initials: R
authors.lastname: Ning
authors.forename: Xianlong
authors.initials: X
authors.lastname: Zhang
authors.forename: Xiaokui
authors.initials: X
authors.lastname: Guo
authors.forename: Qingtian
authors.initials: Q
authors.lastname: Li
mesh_terms: D015153:Blotting, Western; D018932:Chemokine CCL2 / Q000378:metabolism*; D024202:Electrophoretic Mobility Shift Assay; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism*; D007976:Leupeptins / Q000494:pharmacology; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism*; D010006:Osteoblasts / Q000382:microbiology*; D015398:Signal Transduction / Q000502:physiology*; D013211:Staphylococcus aureus / Q000502:physiology*
chemical_list: D018932:Chemokine CCL2; D015850:Interleukin-6; D007976:Leupeptins; D016328:NF-kappa B; C072553:benzyloxycarbonylleucyl-leucyl-leucine aldehyde