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

Jeffrey Schreiber, Philip A. Efron, Julie Park, Lyle L. Moldawer, Adrian Barbul

Research output: Contribution to journalArticle

7 Scopus citations

Abstract

Background. The transcription factor nuclear factor-κB (NF-κB) plays an essential role in inflammation. To date, no studies have investigated the effect of inhibiting NF-κB-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-κB (IκB) into rats undergoing 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-κB (rAd-Iκb), a second group received pumps filled with adenovirus expressing green fluorescent protein (GFP) (rAd-gfp), and a third 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 analyzed for nitrite/nitrate (NOx) and tumor necrosis factor-alpha (TNF-α) concentrations. The wound fluid was assayed for hydroxyproline (OHP) content, an index of reparative collagen deposition. Results. Administration of rAd-Iκb 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-α quantitation analysis found no significant difference among the 3 groups. Conclusion. IκB 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-α independent. Inhibition of NF-κB may reduce inflammation by reducing the local NOx concentrations.

Original languageEnglish (US)
Pages (from-to)940-946
Number of pages7
JournalSurgery
Volume138
Issue number5
DOIs
StatePublished - Nov 1 2005
Externally publishedYes

ASJC Scopus subject areas

  • Surgery

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