Early cutaneous gene transcription changes in adult atopic dermatitis and potential clinical implications.
Atopic dermatitis (AD) is a common pruritic dermatitis with macroscopically non-lesional skin that is often abnormal. Therefore, we used high-density oligonucleotide arrays to identify cutaneous gene transcription changes associated with early AD inflammation as potential disease control targets. Skin biopsy specimens analysed included normal skin from five healthy non-atopic adults and both minimally lesional skin and nearby or contralateral non-lesional skin from six adult AD patients. Data were analysed on an individual gene basis and to identify biologically relevant gene networks. Transcription levels of selected genes were also analysed by quantitative PCR. Differential transcription occurring early in AD skin was indicated for (i) individual genes such as C-C chemokine ligand (CCL)18, CCL13, and interferon-alpha2 (IFNalpha2), (ii) genes associated with peroxisome proliferator-activated receptor (PPAR)alpha- and PPARgamma-regulated transcription, and possibly for (iii) immunoglobulin J-chain and heavy chain isotype transcripts. These data suggest that local changes in immunoglobulin-associated transcription may favour IgE over secretory immunoglobulin (multimeric IgM and IgA) expression in AD skin. Decreased PPAR activity appears common to both AD and psoriasis, and reduced cutaneous IFNalpha2 transcription also appears characteristic of AD. Identification of these genes and pathways will direct future research towards controlling AD.
Plager
Douglas A
DA
Department of Dermatology, Mayo Clinic and Foundation, Rochester, MN 55905, USA. plager.douglas@mayo.edu
Leontovich
Alexey A
AA
Henke
Susan A
SA
Davis
Mark D P
MD
McEvoy
Marian T
MT
Sciallis
Gabriel F
GF
Pittelkow
Mark R
MR
D000328:Adult; D001706:Biopsy; D016022:Case-Control Studies; D019742:Chemokines, CC / Q000235:genetics / Q000378:metabolism; D003876:Dermatitis, Atopic / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D007073:Immunoglobulin E / Q000235:genetics / Q000378:metabolism; D016898:Interferon-alpha / Q000235:genetics / Q000378:metabolism; D008297:Male; D018945:Monocyte Chemoattractant Proteins / Q000235:genetics / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D047493:PPAR alpha / Q000235:genetics / Q000378:metabolism; D047495:PPAR gamma / Q000235:genetics / Q000378:metabolism; D012867:Skin / Q000378:metabolism* / Q000473:pathology; D014158:Transcription, Genetic / Q000235:genetics*
C099677:CCL13 protein, human; C111792:CCL18 protein, human; D019742:Chemokines, CC; D016898:Interferon-alpha; D018945:Monocyte Chemoattractant Proteins; D047493:PPAR alpha; D047495:PPAR gamma; D007073:Immunoglobulin E