title: IL-10 overexpression decreases inflammatory mediators and promotes regenerative healing in an adult model of scar formation.
abstract: Adult wound healing is characterized by an exuberant inflammatory response and scar formation. In contrast, scarless fetal wound healing has diminished inflammation, a lack of fibroplasia, and restoration of normal architecture. We have previously shown that fetal wounds produce less inflammatory cytokines, and the absence of IL-10, an anti-inflammatory cytokine, results in fetal scar formation. We hypothesized that increased IL-10 would decrease inflammation and create an environment conducive for regenerative healing in the adult. To test this hypothesis, a lentiviral vector expressing IL-10 and green fluorescent protein (GFP) (Lenti-IL-10) or GFP alone (Lenti-GFP) was injected at the wound site 48 hours before wounding. We found that both Lenti-IL-10 and Lenti-GFP were expressed in the wounds at 1 and 3 days post wounding. At 3 days, Lenti-IL-10-treated wounds demonstrated decreased inflammation and decreased quantities of all proinflammatory mediators analyzed with statistically different levels of IL-6, monocyte chemoattractant protein-1, and heat-shock protein 47. At 3 weeks, Lenti-GFP wounds demonstrated scar formation. In contrast, wounds injected with Lenti-IL-10 demonstrated decreased inflammation, a lack of abnormal collagen deposition, and restoration of normal dermal architecture. We conclude that lentivirus-mediated overexpression of IL-10 decreases the inflammatory response to injury, creating an environment conducive for regenerative adult wound healing.
authors.affiliation: Department of Surgery, The Center for Fetal Research, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19104-4318, USA.
authors.forename: William H
authors.initials: WH
authors.lastname: Peranteau
authors.forename: Liping
authors.initials: L
authors.lastname: Zhang
authors.forename: Nidal
authors.initials: N
authors.lastname: Muvarak
authors.forename: Andrea T
authors.initials: AT
authors.lastname: Badillo
authors.forename: Antoneta
authors.initials: A
authors.lastname: Radu
authors.forename: Philip W
authors.initials: PW
authors.lastname: Zoltick
authors.forename: Kenneth W
authors.initials: KW
authors.lastname: Liechty
mesh_terms: D000818:Animals; D002921:Cicatrix / Q000503:physiopathology*; D049452:Green Fluorescent Proteins / Q000235:genetics; D050958:HSP47 Heat-Shock Proteins / Q000502:physiology; D007249:Inflammation / Q000517:prevention & control*; D018836:Inflammation Mediators / Q000378:metabolism*; D016753:Interleukin-10 / Q000502:physiology*; D016086:Lentivirus / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D010641:Phenotype; D012038:Regeneration; D014945:Wound Healing / Q000502:physiology*
chemical_list: D050958:HSP47 Heat-Shock Proteins; D018836:Inflammation Mediators; D016753:Interleukin-10; D049452:Green Fluorescent Proteins