title: Wound healing potential of a dimeric InlB variant analyzed by in vitro experiments on re-epithelialization of human skin models.
abstract: A constitutively dimeric truncated variant of internalin B (InlB321-CD), acting as stimulator of the receptor tyrosine kinase MET, was tested for dermal wound-healing potential. Due to a lack of the endogenous MET agonist HGF/SF in chronic wounds, HGF/SF substitution by an InlB321-CD-loaded hydrogel might be beneficial in chronic wound therapy. In this study, InlB321-CD in solution and incorporated in a hydrogel was tested for mitogenic effects on immortalized human dermal keratinocytes (HaCaT) with an MTT assay. Cell migration was investigated with a scratch assay on primary keratinocytes (PHK) and on HaCaT. For the latter, scratching needed to be mitomycin C-controlled. InlB321-CD effects on a model of human skin were analyzed histologically with respect to viability. InlB321-CD led to dose-dependent proliferative effects on HaCaT cells whereas the equimolar dose of monomeric InlB321 did not. Upon hydrogel incorporation of InlB321-CD its mitogenic activity for HaCaT cells was maintained thus confirming the hydrogel as a promising drug delivery system. Motogenic effects were shown on both HaCaT and PHK cells. InlB321-CD neither possesses cytotoxic effects on the viability of a human skin model nor alters its organotypic cell morphology.
authors.affiliation: Institut für Pharmazeutische Technologie, Technische Universität Braunschweig, Braunschweig, Germany.
authors.forename: F
authors.initials: F
authors.lastname: Kolditz
authors.affiliation: Department of Molecular Structural Biology, Helmholtz Centre for Infection Research (HZI), Braunschweig, Germany.
authors.forename: J
authors.initials: J
authors.lastname: Krausze
authors.affiliation: Department of Molecular Structural Biology, Helmholtz Centre for Infection Research (HZI), Braunschweig, Germany.
authors.forename: D W
authors.initials: DW
authors.lastname: Heinz
authors.affiliation: Department of Chemistry and Center for Biotechnology (CeBiTec), Bielefeld University, Bielefeld, Germany.
authors.forename: H H
authors.initials: HH
authors.lastname: Niemann
authors.affiliation: Institut für Pharmazeutische Technologie, Technische Universität Braunschweig, Braunschweig, Germany. Electronic address: C.Mueller-Goymann@tu-braunschweig.de.
authors.forename: C C
authors.initials: CC
authors.lastname: Müller-Goymann
mesh_terms: D001426:Bacterial Proteins / Q000494:pharmacology*; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D005347:Fibroblasts / Q000187:drug effects; D006801:Humans; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate / Q000494:pharmacology; D015603:Keratinocytes / Q000187:drug effects; D008565:Membrane Proteins / Q000494:pharmacology*; D062326:Re-Epithelialization / Q000187:drug effects*; D012867:Skin / Q000187:drug effects*; D012996:Solutions / Q000494:pharmacology; D014945:Wound Healing / Q000187:drug effects*
chemical_list: D001426:Bacterial Proteins; D008565:Membrane Proteins; D012996:Solutions; C095768:inlB protein, Listeria monocytogenes; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate
keywords: 3D skin model; Hydrogel; Internalin B; Keratinocyte; MET receptor; MTT assay; Migration; Proliferation; Scratch assay; Wound healing