Expression of human beta-defensins HBD-1, HBD-2, and HBD-3 in cultured keratinocytes and skin substitutes.
Defensins are effector molecules of the innate host defense system with antimicrobial activity against a variety of pathogens, including microorganisms commonly found in burn units. beta-Defensins are variably expressed in the epithelia of skin and other organs. Cultured skin substitutes (CSS) grafted to burn wounds lack a vascular plexus and are therefore more susceptible to microbial contamination than split thickness skin autograft. To investigate whether beta-defensins can contribute to host defense in CSS, we examined expression of human beta-defensins HBD-1, HBD-2, and HBD-3 in cultured keratinocytes and CSS from uninjured donors and burn patients. HBD-1 was expressed in all keratinocyte strains analyzed. HBD-2 expression in keratinocyte monolayers was highly variable but did not correlate with burn injury. HBD-3 was expressed at variable levels in all but one keratinocyte strain. CSS were prepared from two donors that lacked expression of HBD-2 in keratinocyte monolayers. All three genes were readily detected in CSS from both donors, suggesting up-regulation of HBD-2 and HBD-3. In sections of CSS, HBD-1, HBD-2, and HBD-3 proteins were localized to distinct epidermal regions. We conclude that beta-defensins can potentially contribute to innate immunity in CSS, but their levels may be too low to prevent contamination after grafting.
Research Department, Shriners Hospitals for Children, Cincinnati Burns Hospital, 3229 Burnet Avenue, Cincinnati, OH 45229, USA. dsupp@shrinenet.org
Dorothy M
DM
Supp
Andrea C
AC
Karpinski
Steven T
ST
Boyce
D000293:Adolescent; D000328:Adult; D002056:Burns / Q000378:metabolism* / Q000628:therapy; D002478:Cells, Cultured; D002648:Child; D002675:Child, Preschool; D005260:Female; D015870:Gene Expression; D006801:Humans; D007223:Infant; D015603:Keratinocytes / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000235:genetics; D012867:Skin / Q000378:metabolism; D016038:Skin Transplantation; D017768:Skin, Artificial; D023083:beta-Defensins / Q000235:genetics / Q000378:metabolism*
C406407:DEFB1 protein, human; C422950:DEFB103A protein, human; C106641:DEFB4A protein, human; D012333:RNA, Messenger; D023083:beta-Defensins