Effect of glycyrrhizin on pseudomonal skin infections in human-mouse chimeras.
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-2rγ(null) 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.
Department of Internal Medicine, The University of Texas Medical Branch, Galveston, Texas, United States of America.
Shohei
S
Yoshida
Shriners Hospital for Children, Galveston, Texas, United States of America.
Jong O
JO
Lee
Department of Internal Medicine, The University of Texas Medical Branch, Galveston, Texas, United States of America.
Kiwamu
K
Nakamura
Department of Biostatistics, University of North Texas Health Science Center, Fort Worth, Texas, United States of America.
Sumihiro
S
Suzuki
Shriners Hospital for Children, Galveston, Texas, United States of America.
David N
DN
Hendon
Department of Internal Medicine, The University of Texas Medical Branch, Galveston, Texas, United States of America ; Shriners Hospital for Children, Galveston, Texas, United States of America.
Makiko
M
Kobayashi
Department of Internal Medicine, The University of Texas Medical Branch, Galveston, Texas, United States of America ; Shriners Hospital for Children, Galveston, Texas, United States of America.
Fujio
F
Suzuki
D000276:Adjuvants, Immunologic / Q000494:pharmacology* / Q000627:therapeutic use; D000293:Adolescent; D000328:Adult; D000818:Animals; D002056:Burns / Q000382:microbiology; D002478:Cells, Cultured; D002648:Child; D002675:Child, Preschool; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D019695:Glycyrrhizic Acid / Q000494:pharmacology* / Q000627:therapeutic use; D064593:Heterografts; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000378:metabolism; D008297:Male; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D011552:Pseudomonas Infections / Q000188:drug therapy / Q000276:immunology*; D011550:Pseudomonas aeruginosa / Q000502:physiology*; D018805:Sepsis / Q000382:microbiology / Q000517:prevention & control; D012867:Skin / Q000293:injuries / Q000382:microbiology; D017192:Skin Diseases, Bacterial / Q000188:drug therapy / Q000276:immunology*; D016038:Skin Transplantation; D055815:Young Adult; D023083:beta-Defensins / Q000235:genetics / Q000378:metabolism
D000276:Adjuvants, Immunologic; C406407:DEFB1 protein, human; D023083:beta-Defensins; D019695:Glycyrrhizic Acid