title: Genome-wide expression analysis of human in vivo irritated epidermis: differential profiles induced by sodium lauryl sulfate and nonanoic acid.
abstract: The pathogenesis of irritant contact dermatitis (ICD) is poorly understood, and genes participating in the epidermal response to chemical irritants are only partly known. It is commonly accepted that different irritants have different mechanisms of action in the development of ICD. To define the differential molecular events induced in the epidermis by different irritants, we collected sequential biopsies ((1/2), 4, and 24 hours after a single exposure and at day 11 after repeated exposure) from human volunteers exposed to either sodium lauryl sulfate (SLS) or nonanoic acid (NON). Gene expression analysis using high-density oligonucleotide microarrays (representing 47,000 transcripts) revealed essentially different pathway responses (1/2)hours after exposure: NON transiently induced the IL-6 pathway as well as a number of mitogen-activated signaling cascades including extracellular signal-regulated kinase and growth factor receptor signaling, whereas SLS transiently downregulated cellular energy metabolism pathways. Differential expression of the cyclooxygenase-2 and matrix metalloproteinase 3 transcripts was confirmed immunohistochemically. After cumulative exposure, 883 genes were differentially expressed, whereas we identified 23 suggested common biomarkers for ICD. In conclusion, we bring new insights into two hitherto less well-elucidated phases of skin irritancy: the very initial as well as the late phase after single and cumulative mild exposures, respectively.
authors.affiliation: Department of Dermatology and Allergy Centre, Odense University Hospital, University of Southern Denmark, Odense, Denmark. anders.clemmensen@dadlnet.dk
authors.forename: Anders
authors.initials: A
authors.lastname: Clemmensen
authors.forename: Klaus E
authors.initials: KE
authors.lastname: Andersen
authors.forename: Ole
authors.initials: O
authors.lastname: Clemmensen
authors.forename: Qihua
authors.initials: Q
authors.lastname: Tan
authors.forename: Thomas K
authors.initials: TK
authors.lastname: Petersen
authors.forename: Torben A
authors.initials: TA
authors.lastname: Kruse
authors.forename: Mads
authors.initials: M
authors.lastname: Thomassen
mesh_terms: D000328:Adult; D001706:Biopsy; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism; D003877:Dermatitis, Contact / Q000209:etiology / Q000235:genetics* / Q000473:pathology; D004817:Epidermis / Q000187:drug effects* / Q000473:pathology / Q000502:physiology; D005227:Fatty Acids / Q000009:adverse effects*; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D055106:Genome-Wide Association Study; D006801:Humans; D007150:Immunohistochemistry; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D007509:Irritants / Q000009:adverse effects*; D008297:Male; D019278:Matrix Metalloproteinase 3 / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D012967:Sodium Dodecyl Sulfate / Q000009:adverse effects*; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology
chemical_list: D005227:Fatty Acids; C508600:IL6 protein, human; D015850:Interleukin-6; D007509:Irritants; D012967:Sodium Dodecyl Sulfate; C008776:pelargonic acid; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; C511768:MMP3 protein, human; D019278:Matrix Metalloproteinase 3