Adenoviral gene transfer of an NF-κB super-repressor increases collagen deposition in rodent cutaneous wound healing

Background. The transcription factor nuclear factor-kappa B (NF-kappa B) plays an essential role in inflammation. To date, no studies have investigated the effect of inhibiting NF-kappa B-mediated inflammation on normal cutaneous wound healing. We tested this by locally administering an adenovirus recombinant that constitutively expresses a super-repressor isoform of inhibitory-kappa B (I kappa B) into rats undergoind a well-established model of dorsal wound healing. Methods. Seventy-two Sprague-Dawley rats underwent insertion of a sponge-pump construct into a dorsal subcutaneous pocket. One group of rats received pumps filled with the adenovirus expressing I-kappa B (rAd-I kappa b), a second group received pumps filled with normal saline (NS). Rats were killed in groups of 6 on days 1, 3 , 5 and 7 postoperation. The wound fluid was analysed for nitrite/nitrate (NOx) and tumor necrosis factor-alpha (TNF-alpha) concentrations. The wound fluid was assayed for hydroproline (OHP) content, an index of reparative collagen deposition. Results. Administration of rAd-I kappa B for 7 days resulted in higher collagen deposition (OHP) compared with the rAd-gfp and NS groups. NOx levels were significantly higher in the rAd-gfp group on day 1 and marginally so on day 5. TNF-alpha quantitation analysis found no significant difference among the 3 groups. Conclusion. I kappa B expression through an adenoviral vector in the cutaneous wound may improve rodent healing, as shown by increased collagen deposition, through decreased inflammation. This mechanism appears to be TNF-alpha independent. Inhibition of NF-kappa B may reduce inflammation by reducing the local NOx concentrations.