ArrayExpress Uploader07416IMO-8400IL23 induced phenotypeIMO-8400IL23 induced phenotypeIMO-8400IL23 induced phenotypeIMO-8400IL23 induced phenotypeIMO-8400IL23 induced phenotypeIMO-3100IL23 induced phenotypeIMO-3100IL23 induced phenotypeIMO-3100IL23 induced phenotypeIMO-3100IL23 induced phenotypeIMO-3100IL23 induced phenotypesalineIL23 induced phenotypesalineIL23 induced phenotypesalineIL23 induced phenotypesalineIL23 induced phenotypesalineIL23 induced phenotypena�venormalna�venormalna�venormalna�venormalna�venormalarrayexpress_sid6Psoriasis is a complex inflammatory disease resulting from the activation of T helper (Th) 1 and Th17 cells. Recent evidence suggests...24386404/profile/8773/arrayexpressuploader220diseasekeratinpsoriasisskinDec.12, 2014FalseE-GEOD-50400_A-AFFY-45suppression-of-molecular-inflammatory-pathways-byhttp://www.ebi.ac.uk/arrayexpress/experiments/E-GEOD-50400Suppression of molecular inflammatory pathways by Toll-like Receptor 7, 8, and 9 antagonists in a model of IL-23-induced skin inflammationNov.12, 2014Psoriasis is a complex inflammatory disease resulting from the activation of T helper (Th) 1 and Th17 cells. Recent evidence suggests that abnormal activation of Toll-like receptors (TLRs) 7, 8 and 9 contributes to the initiation and maintenance of psoriasis. We have evaluated the effects of TLR antagonists on the gene expression profile in an IL-23-induced skin inflammation model in mice. Psoriasis-like skin lesions were induced in C57BL/6 mice by intradermal injection of IL-23 in the dorsum. Two TLR antagonists were compared: IMO-3100, an antagonist of TLRs 7 and 9, and IMO-8400, an antagonist of TLRs 7, 8 and 9, both of which previously have been shown to reduce epidermal hyperplasia in this model. Skin gene expression profiles of IL-23-induced inflammation were compared with or without TLR antagonist treatment. IL-23 injection resulted in alteration of 5100 gene probes (fold change ≥ 2, FDR < 0.05) including IL-17 pathways that are up-regulated in psoriasis vulgaris. Targeting TLRs 7, 8 and 9 with IMO-8400 resulted in modulation of more than 2300 mRNAs while targeting TLRs 7 and 9 with IMO-3100 resulted in modulation of more than 1900 mRNAs. Both agents strongly decreased IL-17A expression (>12-fold reduction), normalized IL-17 induced genes such as beta-defensin and CXCL1, and normalized aberrant expression of keratin 16 (indicating epidermal hyperplasia). These results suggest that IL-23-driven inflammation in mouse skin may be dependent on signaling mediated by TLRs 7, 8, and 9 and that these receptors represent novel therapeutic targets in psoriasis vulgaris and other diseases with similar pathophysiology. Expression profiles for mice with IL23-induced phenotype (psoriasisform) at baseline and after treatment with two doses of TLR7/8/9 antagonist and saline. Samples for nomal mice are also availableE-GEOD-50400mousehttp://www.ebi.ac.uk/arrayexpress/experiments/E-GEOD-50400/samples/