Yersinia enterocolitica leads to transient induction of TNF-alpha and activates NF-kB in synovial fibroblasts

A. Meyer-Bahlburg1, S. Greil1, N. Kruse2, R. Marienfeld3, E. Serfling3, H.-I. Huppertz1,4

1Children's Hospital, 2Department of Neurology, and 3Institute of Pathology, University of Würzburg; 4Children's Hospital, University of Göttingen, Göttingen, Germany. 

ABSTRACT
Objective
The importance of the presence of bacterial antigen or even living bacteria for the pathogenesis of reactive arthritis has been discussed increasingly ever since bacterial antigen was found in inflamed joints. Bacteria may persist in the body and drive the local immune response, maintaining arthritis. Cytokines, in particular tumor necrosis factor-a (TNF-a), are essential for bacterial elimination. In reactive arthritis, the course of the disease is influenced by several cytokines, including TNF-a. TNF-a expression can be mediated by transcription factor nuclear factor-kappa B (NF-kB). Moreover, TNF-a is also one of the strongest activators of NF-kB. 

Methods
In vitro expression of TNF-a and activation of NF-kB in synovial fibroblasts after infection with Yersinia enterocolitica or Salmonella enteritidis was analysed by electrophoretic mobility shift assay, Western blot assay and real-time PCR. 

Results
We found that infection of synovial fibroblasts with yersiniae and salmonellae lead to the transient expression of TNF-a mRNA and induction of NF-kB.

Conclusion
Induction of TNF-a in synovial fibroblasts after infection with yersiniae or salmonellae might be insufficient to eliminate bacteria, and this could allow the intracellular persistence of these bacteria. Our results therefore support the hypothesis that a permissive cytokine pattern might contribute to the pathogenesis of reactive arthritis.

Key words
Reactive arthritis, TNF-a, NF-kB, Yersinia enterocolitica, Salmonella enteritidis, pathogenesis.

This study was supported by theBundesministerium fŸr Forschung und Techno-logie (IZKF, project A2).
Please address correspondence to: Hans-Iko Huppertz, MD, Prof.-Hess-Kinderklinik, Klinikum Bremen-Mitt, Sankt-Jürgen-Strasse, 28205 Bremen, Germany. 
E-mail: huppertz.bremen@t-online.de

Clin Exp Rheumatol 2004; 22: 278-284.
© Copyright Clinical and Experimental Rheumatology 2004.