Permissive environment in postnatal wounds induced by adenoviral-mediated overexpression of the anti-inflammatory cytokine interleukin-10 prevents scar formation.
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.
Gordon
Ashley
A
Center for Molecular Fetal Therapy, Division of General, Thoracic and Fetal Surgery, Cincinnati Children's Hospital Medical Center, University of Cincinnati College Of Medicine, Cincinnati, Ohio, USA.
Kozin
Elliott D
ED
Keswani
Sundeep G
SG
Vaikunth
Sachin S
SS
Katz
Anna B
AB
Zoltick
Philip W
PW
Favata
Michele
M
Radu
Antoneta P
AP
Soslowsky
Louis J
LJ
Herlyn
Meenhard
M
Crombleholme
Timothy M
TM
D000256:Adenoviridae; D000818:Animals; D001696:Biomechanical Phenomena; D002921:Cicatrix / Q000209:etiology / Q000276:immunology*; D004195:Disease Models, Animal; D005260:Female; D005333:Fetus / Q000276:immunology; D005822:Genetic Vectors; D006801:Humans; D007150:Immunohistochemistry; D007231:Infant, Newborn; D016753:Interleukin-10 / Q000096:biosynthesis*; D051379:Mice; D008810:Mice, Inbred C57BL; D011247:Pregnancy; D012867:Skin / Q000276:immunology*; D012879:Skin Physiological Phenomena / Q000276:immunology; D019076:Transgenes; D014945:Wound Healing / Q000276:immunology*; D014947:Wounds and Injuries / Q000276:immunology*
D016753:Interleukin-10