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Expression of genes encoding antimicrobial proteins and members of the toll‐like receptor/nuclear factor‐κB pathways in engineered human skin
Author(s) -
McFarland Kevin L.,
Klingenberg Jennifer M.,
Boyce Steven T.,
Supp Dorothy M.
Publication year - 2008
Publication title -
wound repair and regeneration
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.847
H-Index - 109
eISSN - 1524-475X
pISSN - 1067-1927
DOI - 10.1111/j.1524-475x.2008.00401.x
Subject(s) - innate immune system , biology , cathelicidin , proinflammatory cytokine , antimicrobial peptides , tumor necrosis factor alpha , immunology , cytokine , toll like receptor , wound healing , pattern recognition receptor , immune system , microbiology and biotechnology , inflammation , antimicrobial
ABSTRACT Skin functions as a first line of defense against microbial invasion. Tissue‐engineered cultured skin substitutes (CSS) are used to aid wound closure in massively burned patients, and have been used to facilitate safe and effective wound closure in adult patients with chronic wounds. Although they contain only two cell types at grafting, they can potentially contribute to innate defense against pathogens and stimulation of adaptive immunity. Gene microarrays were used to identify expression in cultured skin of genes involved in innate and adaptive immune responses, and to evaluate the effects of cytokine stimulation on expression levels. Cultured skin expressed multiple antimicrobial protein genes, including human β defensins 1 and 2 and S100A12. In addition, the antiviral gene APOBEC3G, which was not previously identified in skin, was expressed in CSS and up‐regulated by interleukin‐1α and tumor necrosis factor α. Cathelicidin was not expressed in unstimulated CSS, but was induced by cytokine treatment. Further, genes encoding several proinflammatory cytokines and members of the toll‐like receptor and nuclear factor κ B pathways were expressed in CSS, suggesting that cells in CSS can mediate activation of inflammatory responses. The observed expression patterns indicate that engineered human skin utilizes innate defense mechanisms similar to those reported for native skin. Therefore, regulation of these pathways by cytokine stimulation may offer a mechanism for increasing innate immunity in CSS to combat wound infection after grafting onto patients.