The soluble terminal complement complex (SC5b-9) up-regulates osteoprotegerin expression and release by endothelial cells: Implications in rheumatoid arthritis

Claudio Tripodo, Lucia Rizzi, Tom E. Mollnes, Francesco Tedesco, Francesco Trotta, Gabriella Castellino, Arianna Gonelli, Fleur Bossi, Giorgio Zauli, Paola Secchiero, Federica Corallini

Risultato della ricerca: Articlepeer review

22 Citazioni (Scopus)

Abstract

Objective. Complement activation products contribute to a large number of inflammatory diseases, including RA. We have investigated whether osteoprotegerin (OPG) may concur with the soluble terminal complement complex (SC5b-9) to the inflammatory cascade characterizing RA. Methods. Levels of SC5b-9 and OPG in the plasma and SF of patients with active RA were determined by ELISA. The presence of SC5b-9 and OPG in RA synovial lesions was analysed by immunohistochemistry. Cultured endothelial cells were used for in vitro leucocyte/endothelial cell adhesion assays. In addition, endothelial cells were exposed to SC5b-9 in order to evaluate the effects on the production of OPG protein, as well as the activation of the OPG promoter. Results. Patients affected by active RA are characterized by elevated levels of both SC5b-9 and OPG in plasma and/or SF. Of note, we have observed a co-localization of SC5b-9 and OPG in endothelial cells of post-capillary venules of RA synovial lesions. Data on endothelial cell cultures showed that exposure to SC5b-9 induced the up-regulation of OPG expression/release, stimulating the transcriptional activity of the OPG promoter, and synergized with TNF-α in up-regulating OPG production. Conclusions. Our findings demonstrate that SC5b-9 induces OPG production by endothelial cells and we propose that the SC5b-9-mediated up-regulation of OPG may be an important mechanism whereby complement contributes in promoting and/or enhancing the inflammation in RA. © The Author 2009. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved.
Lingua originaleEnglish
pagine (da-a)293-298
Numero di pagine6
RivistaRheumatology
Volume48
Stato di pubblicazionePublished - 2009

All Science Journal Classification (ASJC) codes

  • Rheumatology
  • Pharmacology (medical)

Fingerprint Entra nei temi di ricerca di 'The soluble terminal complement complex (SC5b-9) up-regulates osteoprotegerin expression and release by endothelial cells: Implications in rheumatoid arthritis'. Insieme formano una fingerprint unica.

Cita questo