Type

Journal Article

Authors

Steven W Kerrigan
Fergal J O'Brien
Timothy J Foster
Cormac McDonnell
Amro Widaa
Tania Claro

Subjects

Biochemistry

Topics
interleukin 1 factor kappa b interleukin 6 tumour necrosis factor receptor activation 1 protein nf kappa b protein binding

Staphylococcus aureus protein A binding to osteoblast tumour necrosis factor receptor 1 results in activation of nuclear factor kappa B and release of interleukin-6 in bone infection. (2012)

Abstract Staphylococcus aureus is the major pathogen among the staphylococci and the most common cause of bone infections. These infections are mainly characterized by bone destruction and inflammation, and are often debilitating and very difficult to treat. Previously we demonstrated that S. aureus protein A (SpA) can bind to osteoblasts, which results in inhibition of osteoblast proliferation and mineralization, apoptosis, and activation of osteoclasts. In this study we used small interfering RNA (siRNA) to demonstrate that osteoblast tumour necrosis factor receptor-1 (TNFR-1) is responsible for the recognition of and binding to SpA. TNFR-1 binding to SpA results in the activation of nuclear factor kappa B (NFκB). In turn, NFκB translocates to the nucleus of the osteoblast, which leads to release of interleukin 6 (IL-6). Silencing TNFR-1 in osteoblasts or disruption of the spa gene in S. aureus prevented both NFκB activation and IL-6 release. As well as playing a key role in proinflammatory reactions, IL-6 is also an important osteotropic factor. Release of IL-6 from osteoblasts results in the activation of the bone-resorbing cells, the osteoclasts. Consistent with our results described above, both silencing TNFR-1 in osteoblasts and disruption of spa in S. aureus prevented osteoclast activation. These studies are the first to demonstrate the importance of the TNFR-1-SpA interaction in bone infection, and may help explain the mechanism through which osteoclasts become overactivated, leading to bone destruction. Anti-inflammatory drug therapy could be used either alone or in conjunction with antibiotics to treat osteomyelitis or for prophylaxis in high-risk patients.
Collections Ireland -> Royal College of Surgeons in Ireland -> PubMed

Full list of authors on original publication

Steven W Kerrigan, Fergal J O'Brien, Timothy J Foster, Cormac McDonnell, Amro Widaa, Tania Claro

Experts in our system

1
Steven W Kerrigan
Royal College of Surgeons in Ireland
Total Publications: 37
 
2
Fergal J O'Brien
Royal College of Surgeons in Ireland
Total Publications: 268
 
3
Timothy Foster
Trinity College Dublin
Total Publications: 103
 
4
Cormac J McDonnell
Royal College of Surgeons in Ireland
Total Publications: 8
 
5
Amro Widaa
Royal College of Surgeons in Ireland
Total Publications: 13
 
6
Tania Claro
Dublin City University
Total Publications: 13