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Iκ‐B Adenoviral Gene Transfer Improves Wound Healing
Author(s) -
Schreiber J,
Efron P,
Park J,
Moldawer L,
Barbul A
Publication year - 2004
Publication title -
wound repair and regeneration
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.847
H-Index - 109
eISSN - 1524-475X
pISSN - 1067-1927
DOI - 10.1111/j.1067-1927.2004.0abstractap.x
Subject(s) - hydroxyproline , wound healing , saline , sponge , inflammation , chemistry , virus , group a , proinflammatory cytokine , andrology , immunology , microbiology and biotechnology , medicine , biology , biochemistry , botany
: One of the earliest events in wound healing and scar formation is the inflammatory phase. Deficient or excessive inflammatory responses result in aberrant healing. NFK‐b is a transcription factor that regulates key genes responsible for multiple intra‐nuclear inflammatory cytokines. When bound to IK‐B, an inhibitory protein, this factor is in an inactive state. We studied the wound healing effects of irreversibly inhibiting the activation of NFK‐b by continuously infusing adenoviral activated IK‐B. Methods : Seventy‐five male Sprague‐Dawley rats underwent subcutaneous implantation of polyvinyl alcohol sponge‐osmotic pump constructs. The pumps were filled with a solution containing a genetically altered adenovirus containing the DNA for continuously activated IK‐B protein. 50 μl of viral transport media containing 5 × 10 9 PFU of virus were delivered to each individual sponges daily. Controls included pumps filled with normal saline in one group or filled with sham virus in another group. Sponges were harvested on days 1,3,5, and 7 post‐implantation. The sponges were analyzed for TNF‐α and nitric oxide (NO) levels, as index of inflammation, as well as for hydroxyproline (OHP) content at seven days, an index of collagen deposition. Results : Treatment with the IK‐B virus resulted in significantly higher levels of OHP after seven days when compared to normal saline and sham virus treated sponges (654 ± 81 vs 546 ± 109 vs 498 ± 123 μg OHP/100 mg sponge, P < 0.05 by ANOVA). Wound fluid NO concentration was significantly lower in the IkB group after 5 days (38 ± 15 vs 55 ± 12 vs 71 ± 27 μM, P < 0.05 by chi‐square). There were no differences in sponge TNF‐α concentrations on days 1,3, and 5. Conclusions : Treatment of wound sponge granulomas with IK‐B increases the amount of collagen deposition after seven days. Reduction of inflammation by inhibiting NF‐KB may be a possible mechanism of action, as reflected in decreased NO wound content.