Mammalian β-defensins are small cationic peptides of approximately 2-6 kDa that have been implicated in mediating innate immune defenses against microbial infection. Previous studies have reported that mouse β-defensin-14 (MBD14), based on structural and functional similarities,
appears to be an ortholog of human β-defensin-3 (HBD-3). The aim of this study was to identify the signaling pathways that contribute to the expression of MBD-14 in mouse osteoblasts (OBs) upon contact with methicillin-resistant Staphylococcus aureus (S. aureus) supernatant
(SAS) to provide a theoretical basis for the use of MDB-14 as a therapeutic agent in the treatment of intramedullary infection with S. aureus in vivo. The bacterial exoproducts released by S. aureus mainly include a large amount of enterotoxins. Using mouse OBs, the release
and regulation of MBD-14 was evaluated by real-time polymerase chain reaction (PCR) and enzymelinked immunosorbent assay (ELISA) following exposure to SAS. The activation of the p38 mitogenactivated protein kinase (MAPK), extracellular signal-regulated kinase (ERK) and nuclear factor-κB
(NF-κB) pathways was determined by western blot analysis. OBs treated with lipopolysaccharide (LPS) were used as the positive control. The results revealed that SAS significantly promoted the phosphorylation of p38 MAPK, NF-κB and the inhibitory subunit of NF-κBα (IκBα)
in a time-dependent manner. The treatment of OBs with SB203580 (an inhibitor of p38 MAPK) and pyrrolidine dithiocarbamate (PDTC, an inhibitor of NF-κB) prior to stimulation with SAS significantly inhibited the phosphorylation and mRNA expression of p38 MAPK and NF-κB p65, simultaneously
reducing the release of MBD-14. Our findings suggest that the release of MBD-14 is mediated at least in part through the activation of p38 MAPK and NF-κB in response to S. aureussecreted bacterial exoproducts. Moreover, our data demonstrate the innate immune capacity of OBs under
conditions of bacterial challenge to enhance the local expression of this MBD-14, a peptide with antistaphylococcal activity.
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Document Type: Research Article
Department of Orthopaedic Surgery, Shanghai Sixth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200233, P.R. China
Department of Orthopaedic Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, P.R. China
January 1, 2013
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The International Journal of Molecular Medicine is a monthly, peer-reviewed journal devoted to the publication of high quality studies related to the molecular mechanisms of human disease. The journal welcomes research on all aspects of molecular and clinical research, ranging from biochemistry to immunology, pathology, genetics, human genomics, microbiology, molecular pathogenesis, molecular cardiology, molecular surgery and molecular psychology.
The International Journal of Molecular Medicine aims to provide an insight for researchers within the community in regard to developing molecular tools and identifying molecular targets for the diagnosis and treatment of a diverse number of human diseases.
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