title: The acceleration of wound healing in primates by the local administration of immunostimulatory CpG oligonucleotides.
abstract: The process of wound healing involves complex interactions between circulating immune cells and local epithelial and endothelial cells. Studies in murine models indicate that cells of the innate immune system activated via their Toll-like receptors (TLR) can accelerate wound healing. This work examines whether immunostimulatory CpG oligodeoxynucleotides (ODN) designed to trigger human immune cells via TLR9 can promote the healing of excisional skin biopsies in rhesus macaques. Results indicate that 'K' type CpG ODN significantly accelerate wound closure in non-human primates (p < 0.05). Contributing to this outcome was a CpG-dependent increase in both the production of basic fibroblast growth factor and in keratinocyte migration. Of interest, IL-1α and TGFα normally present at sites of skin injury facilitated these effects. Current findings support the conclusion that the local administration of CpG ODN may provide an effective strategy for accelerating wound healing in humans.
authors.affiliation: Cancer and Inflammation Program, National Cancer Institute, Frederick, MD 21702, USA.
authors.forename: Masaki
authors.initials: M
authors.lastname: Yamamoto
authors.forename: Takashi
authors.initials: T
authors.lastname: Sato
authors.forename: Joel
authors.initials: J
authors.lastname: Beren
authors.forename: Daniela
authors.initials: D
authors.lastname: Verthelyi
authors.forename: Dennis M
authors.initials: DM
authors.lastname: Klinman
mesh_terms: D000818:Animals; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000235:genetics / Q000378:metabolism; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D006801:Humans; D015603:Keratinocytes / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D008253:Macaca mulatta / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D009838:Oligodeoxyribonucleotides / Q000276:immunology* / Q000494:pharmacology*; D051193:Toll-Like Receptors / Q000276:immunology; D014945:Wound Healing / Q000187:drug effects*
chemical_list: C408982:CPG-oligonucleotide; D009838:Oligodeoxyribonucleotides; D051193:Toll-Like Receptors; D016222:Fibroblast Growth Factor 2