Article Text

PDF

FRI0074 Adenoviral-based overexpression of timp-1 reduces tissue damage in the joints of tnf-a-transgenic mice
  1. G Schett,
  2. S Hayer,
  3. M Tohidast-Akrad,
  4. Q Xu,
  5. G Kollias,
  6. G Steiner,
  7. J Smolen
  1. Department of Rheumatology, University of Vienna, Vienna, Austria

Abstract

Background Rheumatoid arthritis is a prototype of a destructive inflammatory disease. Inflammation triggered by the overexpression of TNF-a is a driving force of this disorder and mediates tissue destruction. The particular impact of TNF-a-induced molecules, such as matrix metalloproteinases, in tissue destruction is however unknown.

Objectives Herein, the effect of an overexpression of tissue inhibitor of metalloproteinases (TIMP)-1, a physiological antagonist of metalloproteinases, was studied in the arthritis model of TNF- a-transgenic mice.

Methods Systemic treatment was carried out by replication-defective adenoviral vectors for TIMP-1 (AdvTIMP1, n = 7) or b-galactosidase (AdvLacZ, n = 6) or phosphate buffered saline (PBS, n = 7), which were applied once at the onset of arthritis. Clinical, serological, radiological and histological outcomes were assessed 18 days after the treatment.

Results The AdvTIMP1 group showed a significantly reduced paw swelling and increased grip strength compared to the two control groups, whereas total body weight, TNF-a and IL-6 levels were similar in all three groups. Radiological assessment revealed a significant reduction of joint destruction in the AdvTIMP1 group; this was confirmed by histological analyses, showing reduced formation of pannus as well as erosions in the AdvTIMP1 group as compared to the AdvLacZ- and PBS- control groups. The formation of arthritis-specific autoantibodies to hnRNP-A2 was not observed in the AdvTIMP1 group but was present in the two control groups.

Conclusion These results indicates a central role of matrix metalloproteinases in TNF-a-mediated tissue damage in vivo and a promising therapeutic role of TIMP-1.

Statistics from Altmetric.com

Request permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.