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Rheumatology Advance Access published online on June 22, 2004

Rheumatology, doi:10.1093/rheumatology/keh267
Rheumatology © British Society for Rheumatology 2004; all rights reserved
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Received January 13, 2004
Accepted May 13, 2004

Original Papers

Enhanced DNA-dependent protein kinase activity in Sjögren's syndrome B cells

G. Henriksson 1*, A. Sallmyr 1, L. Du 1, Å. Larsson 2, R. Manthorpe 3, A. Bredberg 1

1 Department of Medical Microbiology, Lund University, Malmö University Hospital, Malmö, Sweden
2 Department of Oral Pathology, Centre for Oral Health Sciences, Lund University, Malmö University Hospital, Malmö, Sweden
3 Department of Rheumatology, Sjögren's Syndrome Research Centre, Lund University, Malmö University Hospital, Malmö, Sweden

* To whom correspondence should be addressed. E-mail: gunnel.henriksson{at}mikrobiol.mas.lu.se.


   Abstract

Objective. To examine the stress response, including the role of DNA-dependent protein kinase (DNA-PK), in B cells from Sjögren's syndrome (SS) patients.

Methods. B-cell lines were exposed to gamma radiation and then postincubated to allow inducible stress functions to develop. The magnitude of the DNA damage response was monitored with respect to DNA-PK phosphorylation of a p53 peptide, defence protein levels (Ku, DNA-PK catalytic subunit, ATM, p21 and p53) and flow cytometric determination of cell cycle phases and apoptosis.

Results. B cells from SS patients, compared with healthy controls, displayed enhancement of two stress functions in undamaged cells: DNA-PK kinase activity and apoptosis. In addition, SS showed enhanced cell cycle arrest in gamma-irradiated cells.

Conclusions. Strong kinase activity of DNA-PK, functioning not only in a DNA damage response but also in immunoglobulin gene rearrangement, may be an important component of the heightened stress response displayed by SS cells. In combination with recent reports, our data indicate that constitutional hyper-reactivity to danger signals is a basic pathogenetic factor in SS.

Keywords: Sjögren's syndrome; DNA-dependent protein kinase; Ku protein; Stress response; Cell cycle arrest
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A. Bredberg, G. Henriksson, A. Larsson, R. Manthorpe, and A. Sallmyr
Sjogren's syndrome and the danger model
Rheumatology, August 1, 2005; 44(8): 965 - 970.
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