Allergens and irritants transcriptionally upregulate CD80 gene expression in human keratinocytes.
The human CD80 costimulatory molecule is an important signal between professional antigen-presenting cells and T helper cells. The immunobiology of CD80 expression by keratinocytes, especially during allergic and irritant contact dermatitis, however, is less well understood. CD80 cell surface expression and gene transcription by keratinocytes was increased when keratinocytes were exposed to certain allergens (chemicals that induce inflammation via hapten-specific T cells) and irritants (chemicals that are toxic to epidermal cells). Therefore, the human CD80 promoter was cloned and luciferase reporter constructs containing various promoter fragments were engineered. Promoter mapping of these CD80 constructs in transiently transfected keratinocytes showed that a construct containing the proximal 231 bp immediately upstream of the transcription start site of the CD80 promoter was most active in keratinocytes and was inducible to a level ranging from 2- to 10-fold higher in keratinocytes treated with certain allergens and irritants, compared with untreated keratinocytes. This pattern of promoter fragment activity in keratinocytes is identical to that found in professional antigen-presenting cells. This is the first demonstration that the CD80 promoter is active in keratinocytes and that this activity is further increased in keratinocytes treated with certain allergens and irritants. These data suggest that allergens and irritants may, in part, break peripheral tolerance by their direct effects on keratinocyte costimulatory molecule expression, thereby facilitating interactions with epidermotropic T helper cells via the CD80-CD28 or CTLA-4 pathways.
Wakem
P
P
Department of Dermatology, University of Rochester Medical Center, NY 14642, USA.
Burns
R P
RP
Ramirez
F
F
Zlotnick
D
D
Ferbel
B
B
Haidaris
C G
CG
Gaspari
A A
AA
D000485:Allergens / Q000494:pharmacology*; D000938:Antigen-Presenting Cells / Q000276:immunology; D018122:B7-1 Antigen / Q000235:genetics* / Q000502:physiology*; D002874:Chromosome Mapping; D017449:Dermatitis, Allergic Contact / Q000209:etiology / Q000473:pathology; D006801:Humans; D007231:Infant, Newborn; D007371:Interferon-gamma / Q000494:pharmacology; D007509:Irritants / Q000494:pharmacology*; D015603:Keratinocytes / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D009532:Nickel / Q000276:immunology; D011401:Promoter Regions, Genetic / Q000235:genetics; D012967:Sodium Dodecyl Sulfate / Q000494:pharmacology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014158:Transcription, Genetic / Q000502:physiology; D015854:Up-Regulation / Q000187:drug effects / Q000235:genetics
D000485:Allergens; D018122:B7-1 Antigen; D007509:Irritants; D012967:Sodium Dodecyl Sulfate; C022838:nickel chloride; D009532:Nickel; D007371:Interferon-gamma; D013755:Tetradecanoylphorbol Acetate