title: Early Activation of Th2/Th22 Inflammatory and Pruritogenic Pathways in Acute Canine Atopic Dermatitis Skin Lesions.
abstract: Determining inflammation and itch pathway activation in patients with atopic dermatitis (AD) is fraught with the inability to precisely assess the age of skin lesions, thus affecting the analysis of time-dependent mediators. To characterize inflammatory events occurring during early experimental acute AD lesions, biopsy samples were collected 6, 24, and 48 hours after epicutaneous application of Dermatophagoides farinae house dust mites to sensitized atopic dogs. The skin transcriptome was assessed using a dog-specific microarray and quantitative PCR. Acute canine AD skin lesions had a significant up-regulation of genes encoding T helper (Th) 2 (e.g., IL4, IL5, IL13, IL31, and IL33), Th9 (IL9), and Th22 (IL22) cytokines as well as Th2-promoting chemokines such as CCL5 and CCL17. Proinflammatory (e.g., IL6, LTB, and IL18) cytokines were also up-regulated. Other known pruritogenic pathways were also activated: there was significant up-regulation of genes encoding proteases cathepsin S (CTSS), mast cell chymase (CMA1), tryptase (TPS1) and mastin, neuromedin-B (NMB), nerve growth factor (NGF), and leukotriene-synthesis enzymes (ALOX5, ALOX5AP, and LTA4H). Experimental acute canine house dust mite-induced AD lesions exhibit an activation of innate and adaptive immune responses and pruritogenic pathways similar to those seen in humans with acute AD, thereby validating this model to test innovative therapeutics modalities for this disease.
authors.affiliation: Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, North Carolina, USA; Comparative Medicine Institute, North Carolina State University, Raleigh, North Carolina, USA.
authors.forename: Thierry
authors.initials: T
authors.lastname: Olivry
authors.affiliation: Computational Biology, Target Sciences, GlaxoSmithKline, King of Prussia, Pennsylvania, USA.
authors.forename: David
authors.initials: D
authors.lastname: Mayhew
authors.affiliation: Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, North Carolina, USA.
authors.forename: Judy S
authors.initials: JS
authors.lastname: Paps
authors.affiliation: Comparative Medicine Institute, North Carolina State University, Raleigh, North Carolina, USA; Department of Population Health and Pathobiology, College of Veterinary Medicine, Research Triangle Park, North Carolina, USA.
authors.forename: Keith E
authors.initials: KE
authors.lastname: Linder
authors.affiliation: Stiefel, GlaxoSmithKline, Research Triangle Park, North Carolina, USA. Electronic address: carlos.x.peredo@stiefel.com.
authors.forename: Carlos
authors.initials: C
authors.lastname: Peredo
authors.affiliation: Safety Assessment, Platform Technology and Science, GlaxoSmithKline, Research Triangle Park, NC, USA.
authors.forename: Deepak
authors.initials: D
authors.lastname: Rajpal
authors.affiliation: Stiefel, GlaxoSmithKline, Research Triangle Park, North Carolina, USA.
authors.forename: Hans
authors.initials: H
authors.lastname: Hofland
authors.affiliation: Stiefel, GlaxoSmithKline, Research Triangle Park, North Carolina, USA.
authors.forename: Javier
authors.initials: J
authors.lastname: Cote-Sierra
mesh_terms: D056704:Adaptive Immunity / Q000276:immunology; D000818:Animals; D016207:Cytokines / Q000235:genetics / Q000276:immunology; D003876:Dermatitis, Atopic / Q000276:immunology*; D040001:Dermatophagoides farinae / Q000276:immunology*; D004195:Disease Models, Animal; D004285:Dogs; D005260:Female; D007113:Immunity, Innate / Q000276:immunology; D007249:Inflammation / Q000276:immunology; D016906:Interleukin-9 / Q000235:genetics / Q000276:immunology; D007378:Interleukins / Q000235:genetics / Q000276:immunology*; D008297:Male; D011537:Pruritus / Q000276:immunology; D012867:Skin / Q000276:immunology* / Q000473:pathology; D013045:Species Specificity; D018418:Th2 Cells / Q000276:immunology*; D013997:Time Factors; D015854:Up-Regulation / Q000235:genetics; D000097043:Interleukin-22
chemical_list: D016207:Cytokines; D016906:Interleukin-9; D007378:Interleukins; D000097043:Interleukin-22