title: Extracellular matrix-derived tripeptide proline-glycine-proline inhibits keratinocyte proliferation and migration.
abstract: Keratinocytes are the predominant cell type in epidermis, and are primarily responsible for the epithelialization phase of wound healing. Previous studies by our group showed a positive correlation between IL-8 concentration and delayed healing of porcine cutaneous partial-thickness wounds. Interleukin-8 and collagen-breakdown product N-acetyl-Pro-Gly-Pro (PGP) are known as chemoattractant molecules for neutrophils during inflammation. The activity of both molecules is dependent on chemokine receptors CXCR1 and CXCR2. In addition to neutrophils, keratinocytes also express CXCR1 and CXCR2. Here we investigated the effects of IL-8 and PGP on keratinocyte proliferation and migration. Our results showed that IL-8 up to 100 ng/mL does not have any significant impact on keratinocyte proliferation or migration. ECM-derived tripeptide PGP chemotactically attracts neutrophils but not keratinocytes. PGP strongly inhibits keratinocyte proliferation and migration in a cell-type specific manner. Thus, collagen breakdown product PGP plays a key role in modulating both the inflammatory and epithelialization phases of wound healing.
authors.affiliation: School of Pharmacy, University of Wisconsin-Madison, Wisconsin, USA.
authors.forename: Yiwei
authors.initials: Y
authors.lastname: Ma
authors.forename: Kyle
authors.initials: K
authors.lastname: Kleinbeck
authors.forename: W John
authors.initials: WJ
authors.lastname: Kao
mesh_terms: D002465:Cell Movement / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects*; D002478:Cells, Cultured; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005109:Extracellular Matrix / Q000378:metabolism; D005347:Fibroblasts / Q000187:drug effects / Q000502:physiology; D006801:Humans; D016209:Interleukin-8 / Q000494:pharmacology; D015603:Keratinocytes / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D009504:Neutrophils / Q000187:drug effects / Q000502:physiology; D009842:Oligopeptides / Q000378:metabolism / Q000494:pharmacology*; D011392:Proline / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D023062:Receptors, Interleukin-8A / Q000378:metabolism; D023063:Receptors, Interleukin-8B / Q000378:metabolism; D014945:Wound Healing / Q000502:physiology*
chemical_list: D016209:Interleukin-8; D009842:Oligopeptides; D023062:Receptors, Interleukin-8A; D023063:Receptors, Interleukin-8B; C113164:prolyl-glycyl-proline; D011392:Proline
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