Improved production of human beta-defensins (HBDs) in grafted site skin tissues of human IMC/mouse chimeras treated with glycyrrhizin (GL) (118.14)

Abstract

Abstract Skin HBDs are very important on the elimination of pathogens at the burn wound infections. Immature myeloid cells (IMC) appearing in tissues surrounding the burn area are shown to be inhibitory on skin HBD production. In this study, the effect of GL on the impaired production of skin HBDs was studied in X-irradiated NOD-SCID IL-2rγ−/− mice (NSG mice) grafted with human IMC and their syngeneic skin tissues. NSG mice were grafted with patient skin (8 × 8 mm unburned skin removed for auto-graft surgery; skin-chimeras) and inoculated i.d. with 1 × 106 cells/mouse of CD34+CD31+ IMC isolated from the same burn patients (skin/IMC-chimeras). These chimeras were treated with 0.2 to 40 mg/kg of GL (Minophagen Pharmaceutical CO., LTD., Tokyo, Japan) 6 and 24 hrs after IMC inoculation. Two days after grafting, tissue specimens excised from grafted sites were homogenized, and the amounts of HBDs in the homogenates were measured. In the results, HBD1 and HBD2 were detected in the skin homogenates of skin-chimeras, while the peptides were not detected in the skin homogenates of skin/IMC-chimeras. However, HBDs were detected in the skin homogenates of skin/IMC-chimeras treated i.p. or i.d. with 3 to 10 mg/kg of GL. The greatest efficacy of GL on recovering HBD production was seen when skin/IMC-chimeras were treated i.d. with 10 mg/kg of GL. These results indicate that the impaired HBD production is improved in skin/IMC-chimeras treated with GL.