title: The transcriptional responses of cultured wound cells to the excretions and secretions of medicinal Lucilia sericata larvae.
abstract: Maggots, through their excretions and secretions (ES), promote wound healing by removing necrotic tissue, counter bacterial infection, and activate wound associated cells. We investigated the effects of a physiological dose of maggot ES on four wound-associated cell types in vitro with Affymetrix gene expression arrays; keratinocytes, endothelial cells, fibroblasts, and monocytes. Keratinocytes showed the fewest (n = 5; p < 0.05, fold-change ±2) and smallest fold-changes (up to 2.32×) in gene expression and conversely THP1 monocytes had the most (n = 233) and greatest magnitude (up to 44.3×). There were no genes that were altered in all four cell-lines. Gene pathway analysis identified an enrichment of immune response pathways in three of the treated cell-lines. Analyses by quantitative RT-PCR found many genes dynamically expressed in ES dose dependent manner during the three day treatments. Phenotype analyses, however, found no effects of ES on cell viability, proliferation, migration and angiogenesis. ES was 100× less potent at triggering IL-8 secretion than fibroblasts treated with purified bacterial lipopolysaccharide (LPS; in equivalent amounts to that found in ES; ∼40 EU/ml). Furthermore, co-treatment with LPS and ES decreased the LPS-alone triggered IL-8 secretion by 13%. Although ES had no direct effect on wound cell phenotypes it did partially reduce the immune response to bacterial LPS exposure. These observations were consistent with the profile of transcriptional responses that were dominated by modulation of immune response genes. Maggot therapy may therefore improve wound healing through the secondary effects of these gene changes in the wound cells.
authors.affiliation: Department of Molecular Medicine and Pathology, Faculty of Medical and Health Sciences.|Department of Surgery, Faculty of Medical and Health Sciences.
authors.forename: Priscila
authors.initials: P
authors.lastname: Dauros Singorenko
authors.affiliation: Department of Obstetrics and Gynaecology, Faculty of Medical and Health Sciences.
authors.forename: Roseanne
authors.initials: R
authors.lastname: Rosario
authors.affiliation: Department of Surgery, Faculty of Medical and Health Sciences.|Maurice Wilkins Centre for Biodiscovery, University of Auckland.
authors.forename: John A
authors.initials: JA
authors.lastname: Windsor
authors.affiliation: Department of Surgery, Faculty of Medical and Health Sciences.|Maurice Wilkins Centre for Biodiscovery, University of Auckland.|School of Biological Sciences, University of Auckland, Auckland, New Zealand.
authors.forename: Anthony R
authors.initials: AR
authors.lastname: Phillips
authors.affiliation: Department of Molecular Medicine and Pathology, Faculty of Medical and Health Sciences.|Department of Surgery, Faculty of Medical and Health Sciences.|School of Biological Sciences, University of Auckland, Auckland, New Zealand.
authors.forename: Cherie
authors.initials: C
authors.lastname: Blenkiron
mesh_terms: D000818:Animals; D012634:Bodily Secretions / Q000378:metabolism; D002460:Cell Line; D002478:Cells, Cultured; D004175:Diptera; D042783:Endothelial Cells / Q000502:physiology*; D005347:Fibroblasts / Q000502:physiology*; D020869:Gene Expression Profiling; D066298:In Vitro Techniques; D015603:Keratinocytes / Q000502:physiology*; D007814:Larva / Q000378:metabolism* / Q000502:physiology; D009000:Monocytes / Q000502:physiology*; D014158:Transcription, Genetic / Q000502:physiology; D014945:Wound Healing / Q000235:genetics* / Q000276:immunology