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

Kizzie Manning, P. Sivaramakrishna Rachakonda, Muhammad Farooq Rai, Michael F.G. Schmidt

Research output: Contribution to journalArticlepeer-review

13 Scopus citations

Abstract

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-1β and TNFα, 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.

Original languageEnglish
Pages (from-to)297-305
Number of pages9
JournalCytokine
Volume50
Issue number3
DOIs
StatePublished - Jun 2010

Keywords

  • Arthritis
  • IGF-1
  • IL-4
  • Inflammation
  • Pro-inflammatory cytokines

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