title: Oestrogen promotes healing in a bacterial LPS model of delayed cutaneous wound repair.
abstract: Wound infection is a major clinical problem, yet understanding of bacterial host interactions in the skin remains limited. Microbe-derived molecules, known as pathogen-associated molecular patterns, are recognised in barrier tissues by pattern-recognition receptors. In particular, the pathogen-associated molecular pattern, lipopolysaccharide (LPS), a component of microbial cell walls and a specific ligand for Toll-like receptor 4, has been widely used to mimic systemic and local infection across a range of tissues. Here we administered LPS derived from Klebsiella pneumoniae, a species of bacteria that is emerging as a wound-associated pathogen, to full-thickness cutaneous wounds in C57/BL6 mice. Early in healing, LPS-treated wounds displayed increased local apoptosis and reduced proliferation. Subsequent healing progression was delayed with reduced re-epithelialisation, increased proliferation, a heightened inflammatory response and perturbed wound matrix deposition. Our group and others have previously demonstrated the beneficial effects of 17β-estradiol treatment across a range of preclinical wound models. Here we asked whether oestrogen would effectively promote healing in our LPS bacterial infection model. Intriguingly, co-treatment with 17β-estradiol was able to promote re-epithelialisation, dampen inflammation and induce collagen deposition in our LPS-delayed healing model. Collectively, these studies validate K. pneumoniae-derived LPS treatment as a simple yet effective model of bacterial wound infection, while providing the first indication that oestrogen could promote cutaneous healing in the presence of infection, further strengthening the case for its therapeutic use.
authors: The Healing Foundation Centre, Faculty of Life Sciences, The University of Manchester, Manchester, UK.
authors: Rachel
authors: R
authors: Crompton
authors: The Healing Foundation Centre, Faculty of Life Sciences, The University of Manchester, Manchester, UK.
authors: Helen
authors: H
authors: Williams
authors: The Healing Foundation Centre, Faculty of Life Sciences, The University of Manchester, Manchester, UK.|The Centre for Dermatology Research, Institute of Inflammation and Repair, The University of Manchester, Manchester, UK.
authors: David
authors: http://orcid.org/0000-0002-6977-4288
authors: D
authors: Ansell
authors: The Healing Foundation Centre, Faculty of Life Sciences, The University of Manchester, Manchester, UK.
authors: Laura
authors: L
authors: Campbell
authors: Epistem, Manchester, UK.
authors: Kirsty
authors: K
authors: Holden
authors: Faculty of Life Sciences, The University of Manchester, Manchester, UK.
authors: Sheena
authors: http://orcid.org/0000-0002-3047-5475
authors: S
authors: Cruickshank
authors: The Healing Foundation Centre, Faculty of Life Sciences, The University of Manchester, Manchester, UK.
authors: Matthew J
authors: MJ
authors: Hardman
mesh_terms: D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D004195:Disease Models, Animal; D004958:Estradiol / Q000494:pharmacology; D004967:Estrogens / Q000494:pharmacology*; D005260:Female; D054884:Host-Pathogen Interactions / Q000187:drug effects; D006801:Humans; D015603:Keratinocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D007710:Klebsiella Infections / Q000139:chemically induced / Q000382:microbiology / Q000517:prevention & control*; D007711:Klebsiella pneumoniae / Q000737:chemistry / Q000187:drug effects* / Q000502:physiology; D008070:Lipopolysaccharides; D008810:Mice, Inbred C57BL; D008856:Microscopy, Fluorescence; D012867:Skin / Q000187:drug effects* / Q000382:microbiology / Q000503:physiopathology; D013997:Time Factors; D051197:Toll-Like Receptor 4 / Q000378:metabolism; D014945:Wound Healing / Q000187:drug effects*; D014946:Wound Infection / Q000139:chemically induced / Q000382:microbiology / Q000517:prevention & control*
chemical_list: D004967:Estrogens; D008070:Lipopolysaccharides; D051197:Toll-Like Receptor 4; D004958:Estradiol