Co-expression of insulin-like growth factor-1 and interleukin-4 in an in vitro inflammatory model.

Autor: Manning K; Institute of Immunology and Molecular Biology, Freie Universität Berlin, Philippstrasse 13, 10115 Berlin, Germany., Rachakonda PS, Rai MF, Schmidt MF
Jazyk: angličtina
Zdroj: Cytokine [Cytokine] 2010 Jun; Vol. 50 (3), pp. 297-305. Date of Electronic Publication: 2010 Feb 25.
DOI: 10.1016/j.cyto.2010.01.010
Abstrakt: The ailment osteoarthritis (OA) has two aspects - inflammation and cartilage degradation - where combined transgene expression may offer an effective gene therapy. Our present study focuses on the co-expression of interleukin-4 (IL-4) and insulin-like-growth factor-1 (IGF-1), which specifically target inflammation and cartilage repair, respectively. In this study, we analyze the expression of IGF-1 and IL-4 from a single plasmid vector, where each gene is expressed through an independent promoter and enhancer sequence. Regenerative and anti-inflammatory effects of IGF-1 alone and of both IGF-1 and IL-4 were analyzed in an in vitro chondrocyte inflammatory model. Co-expression of both transgenes in primary chondrocytes was ascertained by immunoassays. Following stimulation with IL-1beta and TNFalpha, pro-inflammatory mediators as well as IGF-binding proteins were down-regulated more effectively in the presence of both genes to levels comparable to the non-stimulated control. Further, cartilage regeneration proteins type II collagen and proteoglycans were up-regulated in stimulated cells transfected with IGF-1 alone and in combination with IL-4. The co-expression of IGF-1 and IL-4 shows that both transgenes complement each other by effectively triggering cartilage regeneration and reducing inflammation. Use of combinatorial transgene expression offers a promising avenue in the area of gene therapy in OA.
(Copyright 2010 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
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