Effect of glycyrrhizin on pseudomonal skin infections in human-mouse chimeras

Shohei Yoshida, Jong Lee, Kiwamu Nakamura, Sumihiro Suzuki, David N. Hendon, Makiko Kobayashi, Fujio Suzuki

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

In our previous studies, peripheral blood lineage -CD34 +CD31+ cells (CD31+ IMC) appearing in severely burned patients have been characterized as inhibitor cells for the production of β-defensins (HBDs) by human epidermal keratinocytes (NHEK). In this study, the effect of glycyrrhizin on pseudomonal skin infections was studied in a chimera model of thermal injury. Two different chimera models were utilized. Patient chimeras were created in murine antimicrobial peptide-depleted NOD-SCID IL-2rγnull mice that were grafted with unburned skin tissues of severely burned patients and inoculated with the same patient peripheral blood CD31+ IMC. Patient chimera substitutes were created in the same mice that were grafted with NHEK and inoculated with experimentally induced CD31 + IMC. In the results, both groups of chimeras treated with glycyrrhizin resisted a 20 LD50 dose of P. aeruginosa skin infection, while all chimeras in both groups treated with saline died within 3 days of the infection. Human antimicrobial peptides were detected from the grafted site tissues of both groups of chimeras treated with glycyrrhizin, while the peptides were not detected in the same area tissues of controls. HBD-1 was produced by keratinocytes in transwell-cultures performed with CD31+ IMC and glycyrrhizin. Also, inhibitors (IL-10 and CCL2) of HBD-1 production by keratinocytes were not detected in cultures of patient CD31+ IMC treated with glycyrrhizin. These results indicate that sepsis stemming from pseudomonal grafted site infections in a chimera model of burn injury is controllable by glycyrrhizin. Impaired antimicrobial peptide production at the infection site of severely burned patients may be restored after treatment with glycyrrhizin.

Original languageEnglish (US)
Article numbere83747
JournalPLoS One
Volume9
Issue number1
DOIs
StatePublished - Jan 30 2014

Fingerprint

glycyrrhizin
Glycyrrhizic Acid
chimerism
skin (animal)
Skin
mice
Infection
infection
antimicrobial peptides
keratinocytes
Keratinocytes
Peptides
Tissue
Blood
Defensins
burns (injuries)
heat injury
sepsis (infection)
Lethal Dose 50
blood

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Effect of glycyrrhizin on pseudomonal skin infections in human-mouse chimeras. / Yoshida, Shohei; Lee, Jong; Nakamura, Kiwamu; Suzuki, Sumihiro; Hendon, David N.; Kobayashi, Makiko; Suzuki, Fujio.

In: PLoS One, Vol. 9, No. 1, e83747, 30.01.2014.

Research output: Contribution to journalArticle

Yoshida S, Lee J, Nakamura K, Suzuki S, Hendon DN, Kobayashi M et al. Effect of glycyrrhizin on pseudomonal skin infections in human-mouse chimeras. PLoS One. 2014 Jan 30;9(1). e83747. https://doi.org/10.1371/journal.pone.0083747
Yoshida, Shohei ; Lee, Jong ; Nakamura, Kiwamu ; Suzuki, Sumihiro ; Hendon, David N. ; Kobayashi, Makiko ; Suzuki, Fujio. / Effect of glycyrrhizin on pseudomonal skin infections in human-mouse chimeras. In: PLoS One. 2014 ; Vol. 9, No. 1.
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abstract = "In our previous studies, peripheral blood lineage -CD34 +CD31+ cells (CD31+ IMC) appearing in severely burned patients have been characterized as inhibitor cells for the production of β-defensins (HBDs) by human epidermal keratinocytes (NHEK). In this study, the effect of glycyrrhizin on pseudomonal skin infections was studied in a chimera model of thermal injury. Two different chimera models were utilized. Patient chimeras were created in murine antimicrobial peptide-depleted NOD-SCID IL-2rγnull mice that were grafted with unburned skin tissues of severely burned patients and inoculated with the same patient peripheral blood CD31+ IMC. Patient chimera substitutes were created in the same mice that were grafted with NHEK and inoculated with experimentally induced CD31 + IMC. In the results, both groups of chimeras treated with glycyrrhizin resisted a 20 LD50 dose of P. aeruginosa skin infection, while all chimeras in both groups treated with saline died within 3 days of the infection. Human antimicrobial peptides were detected from the grafted site tissues of both groups of chimeras treated with glycyrrhizin, while the peptides were not detected in the same area tissues of controls. HBD-1 was produced by keratinocytes in transwell-cultures performed with CD31+ IMC and glycyrrhizin. Also, inhibitors (IL-10 and CCL2) of HBD-1 production by keratinocytes were not detected in cultures of patient CD31+ IMC treated with glycyrrhizin. These results indicate that sepsis stemming from pseudomonal grafted site infections in a chimera model of burn injury is controllable by glycyrrhizin. Impaired antimicrobial peptide production at the infection site of severely burned patients may be restored after treatment with glycyrrhizin.",
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