Interleukin 34 expression is associated with synovitis severity in rheumatoid arthritis patients
- M Chemel1,2,3,
- B Le Goff1,2,3,
- R Brion1,2,3,
- C Cozic1,2,3,
- M Berreur1,2,
- J Amiaud1,2,
- G Bougras1,2,
- S Touchais3,
- F Blanchard1,2,
- M F Heymann1,2,
- J M Berthelot1,2,3,
- F Verrecchia1,2,
- D Heymann1,2,3
- 1INSERM, UMR 957, France
- 2Université de Nantes, Nantes Atlantique Universités, Laboratoire de Physiopathologie de la Résorption Osseuse et Thérapie des Tumeurs Osseuses Primitives, Nantes, France
- 3Pôle Ostéoarticulaire, CHU de Nantes, Nantes, France
- Correspondence to Professor Dominique Heymann, INSERM UMR-S 957, Physiopathologie de la Résorption Osseuse et Thérapie des Tumeurs Osseuses Primitives, Faculté de Médecine, 1 rue Gaston Veil, 44035 Nantes cedex 1, France;
- Received 20 April 2011
- Accepted 20 September 2011
- Published Online First 28 October 2011
Objectives Interleukin (IL) 34 is a new cytokine implicated in macrophage differentiation and osteoclastogenesis. This study assessed IL-34 expression in the tissue of patients with rheumatoid arthritis (RA).
Methods Immunohistochemistry was performed in synovial biopsies from patients with RA (n=20), osteoarthritis (n=3) or other inflammatory arthritis (n=4). IL-34 was detected in the synovial fluid by ELISA and its messenger RNA expression was studied by quantitative PCR in rheumatoid synovial fibroblasts after stimulation by tumour necrosis factor α (TNFα) and IL-1β. Wild-type, jnk1−/−–jnk2−/− and nemo−/− murine fibroblasts and pharmacological inhibition were used to determine the involvement of nuclear factor kappa B (NF-κB) and JNK in that effect.
Results IL-34 was expressed in 24/27 biopsies, with three samples from RA patients being negative. A significant association was found between IL-34 expression and synovitis severity. Levels of IL-34 and the total leucocyte count in synovial fluid were correlated. TNFα and IL-1β stimulated IL-34 expression by synovial fibroblasts in a dose/time-dependent manner through the NF-κB and JNK pathway.
Conclusion This work for the first time identifies IL-34 expression in the synovial tissue of patients with arthritis. This cytokine, as a downstream effector of TNFα and IL-1β, may contribute to inflammation and bone erosions in RA.
MC and BLG contributed equally to this work.
Funding This work was supported by the ARTHRITIS Fondation Courtin (to JMB).
Competing interests None.
Patient consent Obtained.
Ethics approval The experimental procedures followed were carried out in accordance with the ethical standards of the responsible institutional committee on human experimentation and the Helsinki Declaration. The study was approved by the institutional ethics committee.
Provenance and peer review Not commissioned; externally peer reviewed.