Oestrogen promotes healing in a bacterial LPS model of delayed cutaneous wound repair
Crompton, R. Williams, H. Campbell, Laura Holden, K. Cruickshank, S. Hardman, M.J.
Crompton, R.
Williams, H.
Campbell, Laura
Holden, K.
Cruickshank, S.
Hardman, M.J.
Publication Date
2016-04
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2015-12-11
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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.
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Crompton R, Williams H, Ansell DM, et al (2016) Oestrogen promotes healing in a bacterial LPS model of delayed cutaneous wound repair. Laboratory Investigation, 96: 439-449
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