Rachakonda PS et al. - A construct featuring a truncated promoter sequence of COX-2, upstream of the IL-4 (antiinflammatory gene) allows production of a therapeutic gene product controlled by the severity of the disease. This promoter construct may be a suitable candidate for the development of a new local gene therapy strategy for the treatment of osteoarthritis. Methods
Study to validate a new gene therapy approach using a novel inflammation-responsive promoter construct
A promoter construct was designed to express IL-4 only in the presence of inflammation
Construct featured a truncated promoter sequence of COX-2 upstream of the IL-4 gene
Inflammation was triggered in articular chondrocytes by applying IL-1 and TNF together
Extent of IL-4 expression and its effect on the inflammatory cascade was studied
Results
COX-2 promoter construct expressed IL-4 only in the presence of IL-1 and TNF
IL-4 expressed in the presence of IL-1 and TNF down-regulated a series of inflammation mediators, prostaglandins, and matrix metalloproteinases
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