Apoptosis as a target for gene therapy in rheumatoid arthritis

Authors
Citation
Ga. Rabinovich, Apoptosis as a target for gene therapy in rheumatoid arthritis, MEM I OSW C, 95, 2000, pp. 225-233
Citations number
56
Categorie Soggetti
Medical Research General Topics
Journal title
MEMORIAS DO INSTITUTO OSWALDO CRUZ
ISSN journal
00740276 → ACNP
Volume
95
Year of publication
2000
Supplement
1
Pages
225 - 233
Database
ISI
SICI code
0074-0276(2000)95:<225:AAATFG>2.0.ZU;2-P
Abstract
Rheumatoid arthritis (RA) is characterized by chronic inflammation of the s ynovial joints resulting from hyperplasia of synovial fibroblasts and infil tration of lymphocytes, macrophages and plasma cells, all of which manifest signs of activation. All these cells proliferate abnormally, invade bone a nd cartilage, produce an elevated amount of pro-inflammatory cytokines, met alloproteinases and trigger osteoclast formation and activation. Some of th e pathophysiological consequences of the disease may be explained by the in adequate apoptosis, which may promote the survival of autoreactive T cells, macrophages or synovial fibroblasts Although RA does not result from singl e genetic mutations, elucidation of the molecular mechanisms implicated in joint destruction has revealed novel targets for gene therapy. Gene transfe r strategies include inhibition of pro-inflammatory cytokines, blockade of cartilage-degrading metalloproteinases, inhibition of synovial cell activat ion and manipulation of the Th1-Th2 cytokine balance. Recent findings have iluminated the idea that induction of apoptosis in the rheumatoid joint can be also used to gain therapeutic advantage in the disease. In the present review we will discuss different strategies used for gene transfer in RA an d chronic inflammation. Particularly, we will highlight the importance of p rogrammed cell death as a novel target for gene therapy using endogenous bi ological mediators, such as galectin-1, a beta -galactoside-binding protein that induces apoptosis of activated T cells and immature thymocytes.