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Oestrogen promotes healing in a bacterial LPS model of delayed cutaneous wound repair

Crompton, R.; Williams, H.; Ansell, D.; Campbell, L.; Holden, K.; Cruickshank, S.; Hardman, M. J.


R. Crompton

H. Williams

D. Ansell

L. Campbell

K. Holden

S. Cruickshank


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 17beta-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 17beta-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.


Crompton, R., Williams, H., Ansell, D., Campbell, L., Holden, K., Cruickshank, S., & Hardman, M. J. (2016). Oestrogen promotes healing in a bacterial LPS model of delayed cutaneous wound repair. Laboratory investigation, 96(4), 439-449.

Journal Article Type Article
Acceptance Date Dec 11, 2015
Online Publication Date Feb 8, 2016
Publication Date 2016-04
Deposit Date Jan 25, 2021
Journal Laboratory investigation; a journal of technical methods and pathology
Print ISSN 0023-6837
Publisher Nature Publishing Group
Peer Reviewed Peer Reviewed
Volume 96
Issue 4
Pages 439-449
ISBN 1530-0307
Keywords Infection; Mechanisms of disease; Toll-like receptors
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