Effects of lipopolysaccharide and CpG-DNA on burn-induced skin injury

Kim, Dongbum; Cho, Sunhee; Seo, Jae-Nam; Park, Jae-Bong; Kim, Yong-Sun; Choi, Ihn-Geun; Kwon, Hyeok-Yil; Lee, Younghee; Kwon, Hyung‐Joo

doi:10.5483/bmbrep.2011.44.4.273

Cited by 5 publications

(3 citation statements)

References 39 publications

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“…We note that our observed phenotype is in agreement with other local and systemic LPS administration models. For example, local and systemic LPS as a model of infection in burn injury induced a heightened inflammatory response and epidermal thickening, 35,55,56 whereas decreased collagen deposition was observed with systemic administration of LPS in cutaneous rat wounds. 57 Crucially, we demonstrate the utility of LPS administration as a delayed healing model by showing that co-administration of the pleiotropic healing-promoting factor 17β-estradiol is able to reverse some, but not all, aspects of the LPS healing phenotype.…”

Section: Oestrogen Restores Healing In Lps Model R Crompton Et Almentioning

confidence: 99%

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

Crompton

Williams

Ansell

et al. 2016

Laboratory Investigation

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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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Section: Oestrogen Restores Healing In Lps Model R Crompton Et Almentioning

confidence: 99%

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

Crompton

Williams

Ansell

et al. 2016

Laboratory Investigation

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“…In detail, 50% wound closure could be achieved at ∼4 days in CpG‐treated mice in contrast to ∼7 days in control ODN‐treated animals . While repetitive topical application of high doses of CpG ODN might result in an overwhelming activation of the innate immune system and, thus, deterioration of skin healing, deliberate activation of the immune system by a single topical application of a lower dose of CpG ODN may be beneficial and turn into an acceleration of skin wound healing . We could now show that even the pretreatment strategy with CpG‐induced priming of innate immune system 6 days prior wounding improves wound epithelialization constantly.…”

Section: Discussionmentioning

confidence: 84%

“…It is important to mention that the effect of CpG ODN seems to be highly dependent on the time point and regimen of application. CpG ODN, topically applied to the dorsal skin of mice for 5 days at a dose of 2.5 mg/kg each after thermal injury (equivalent to 75 μg/mouse, assuming a body weight of 30 g), delayed spontaneous healing and increased pro‐inflammatory cytokine gene expression . In contrast, the coverage of full thickness wounds in mice with a gel of basement membrane extract (BME) containing 50 μg CpG ODN caused a 44% faster healing compared with untreated wounds or wounds covered with BME and control ODN .…”

Section: Discussionmentioning

confidence: 99%

Effects of systemic pretreatment with CpG oligodeoxynucleotides on skin wound healing in mice

Hergert

Grambow

Butschkau

et al. 2013

Wound Repair Regeneration

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Unmethylated CpG oligodeoxynucleotides (ODN) bind to the Toll-like receptor 9, thus stimulating the immune system. To study the effects of systemic pretreatment with CpG ODN on dermal regeneration, C57BL6/J Tyr mice were treated with CpG or control ODN 6 days prior to implantation of a dorsal skinfold chamber and skin wounding. Wound epithelialization was analyzed by planimetric microscopy. On day 18, wound tissues were taken for (immuno)histochemical staining. CpG ODN increased epithelialization compared with control ODN treatment. Histological analysis revealed reduced capillary density, reduced wound cellularity, and reduced numbers of infiltrating leukocytes, as well as reduced F4/80-positive macrophages, but increased numbers of RELM-α-positive M2 macrophages after CpG ODN treatment, reflecting a better quality of wound healing on day 18 compared with control ODN treatment. Reverse transcription-polymerase chain reaction analysis of Toll-like receptor 9 showed the receptor expression on both fibroblasts and keratinocytes. Fibroblasts showed an increase of migration upon increasing dosages of CpG and not control ODN, reaching ∼50% of the response of basic fibroblast growth factor-exposed cells. Keratinocytes dose-dependently responded to both CpG and control ODN up to values found in keratinocyte growth factor-exposed cells. In summary, CpG ODN support late tissue-remodeling processes that contribute to resolution of inflammation and solid wounds during skin regeneration.

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The role of hydrogen sulfide in burns

Akter

2016

Burns

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Effects of lipopolysaccharide and CpG-DNA on burn-induced skin injury

Cited by 5 publications

References 39 publications

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

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

Effects of systemic pretreatment with CpG oligodeoxynucleotides on skin wound healing in mice

The role of hydrogen sulfide in burns

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