Permissive environment in postnatal wounds induced by adenoviral-mediated overexpression of the anti-inflammatory cytokine interleukin-10 prevents scar formation.

Abstract

Wound healing in the mid-gestation fetus is scarless with minimal inflammation and a unique extracellular matrix. We have previously documented the relative lack of inflammatory cytokines in this environment. We demonstrate that interleukin (IL)-10 is highly expressed in mid-gestation human fetal skin but is absent in postnatal human skin. We hypothesize that overexpression of IL-10 in postnatal skin may replicate a permissive environment for scarless healing. To study the mechanism underlying this process we performed immunohistochemistry for IL-10 in human mid-gestation fetal and postnatal skin. We also determined if adenoviral-mediated overexpression of IL-10 could allow for scarless wound healing in a murine incisional wound model. Wounds were analyzed at 1-90 days postwounding for effects on scar formation, inflammatory response, and biomechanical properties. Ad-IL-10 reconstitutes a permissive environment for scarless healing as shown by reconstitution of a normal dermal reticular collagen pattern and distribution of dermal elements. Compared with controls, Ad-IL-10 treated wounds showed reduced inflammatory response and no difference in biomechanical parameters. Therefore, overexpression of IL-10 in postnatal wounds results in a permissive environment for scarless wound repair, possibly by replicating a fetal wound environment.

• Authors: Ashley Gordon, Elliott D Kozin, Sundeep G Keswani, Sachin S Vaikunth, Anna B Katz, Philip W Zoltick, Michele Favata, Antoneta P Radu, Louis J Soslowsky, Meenhard Herlyn, Timothy M Crombleholme
• Journal: Wound repair and regeneration : official publication of the Wound Healing Society [and] the European Tissue Repair Society (Wound Repair Regen) 2008 Jan-Feb Vol. 16 Issue 1 Pg. 70-9 ISSN: 1524-475X [Electronic] United States
• PMID: 18086289 (Publication Type: Journal Article)

Chemical References

• Interleukin-10

Topics

• Adenoviridae
• Animals
• Biomechanical Phenomena
• Cicatrix (etiology, immunology)
• Disease Models, Animal
• Female
• Fetus (immunology)
• Genetic Vectors
• Humans
• Immunohistochemistry
• Infant, Newborn
• Interleukin-10 (biosynthesis)
• Mice
• Mice, Inbred C57BL
• Pregnancy
• Skin (immunology)
• Skin Physiological Phenomena (immunology)
• Transgenes
• Wound Healing (immunology)
• Wounds and Injuries (immunology)