OBJECTIVES: To investigate Toll-like receptor activation in human skin using tape stripping and imiquimod cream challenges in healthy volunteers. SUBJECTS, TREATMENT AND METHODS: Seventeen male Caucasian subjects underwent a baseline biopsy on their lower back prior to two tape stripping procedures 7 days apart. Subjects were then treated with 5% imiquimod for 2 and 4 days on separate sites in the same area. Further biopsies were taken 22-24 h after each challenge and mRNA and microRNA extracted and expression values analysed using robust statistical and pathway analysis methods. RESULTS: Fifteen of the 17 subjects completed the study according to protocol. No adverse events were associated with the procedures. A significant change (p < 0.05, fold change >1.5 or <-1.5) in mRNA expression of 7,996 genes was evident in biopsies taken at both time points post tape stripping, compared to baseline biopsy expression values. The induction of mRNAs involved in various pathways including adhesion and migration was evident. mRNA markers representing inflammatory cells [e.g., CD14, CD3E (p < 0.0001)] and mRNAs encoding genes regulated by type 1 interferon (IFN) [e.g., MX1, OAS1and CXCL10 (p < 0.0001)] were significantly up-regulated. IFNα and CXCL10 proteins were detectable in exudates released 1 and 4 h post tape stripping. A putative signalling network associating these transcripts and six microRNAs (hsa-miR, -31, -132, -155, 548c, 548n and 574) was identified using a meta-regulation network model. microRNAs not previously associated with IFN signalling have been identified. In contrast, only 223 known transcripts were significantly changed after imiquimod treatment, including CXCL10, and OAS1. CONCLUSION: Results suggest that IFN signalling is important in these translational models and novel miRNA may be new targets in the treatment of IFN associated skin disease.
OBJECTIVES: To investigate Toll-like receptor activation in human skin using tape stripping and imiquimod cream challenges in healthy volunteers. SUBJECTS, TREATMENT AND METHODS: Seventeen male Caucasian subjects underwent a baseline biopsy on their lower back prior to two tape stripping procedures 7 days apart. Subjects were then treated with 5% imiquimod for 2 and 4 days on separate sites in the same area. Further biopsies were taken 22-24 h after each challenge and mRNA and microRNA extracted and expression values analysed using robust statistical and pathway analysis methods. RESULTS: Fifteen of the 17 subjects completed the study according to protocol. No adverse events were associated with the procedures. A significant change (p < 0.05, fold change >1.5 or <-1.5) in mRNA expression of 7,996 genes was evident in biopsies taken at both time points post tape stripping, compared to baseline biopsy expression values. The induction of mRNAs involved in various pathways including adhesion and migration was evident. mRNA markers representing inflammatory cells [e.g., CD14, CD3E (p < 0.0001)] and mRNAs encoding genes regulated by type 1 interferon (IFN) [e.g., MX1, OAS1and CXCL10 (p < 0.0001)] were significantly up-regulated. IFNα and CXCL10 proteins were detectable in exudates released 1 and 4 h post tape stripping. A putative signalling network associating these transcripts and six microRNAs (hsa-miR, -31, -132, -155, 548c, 548n and 574) was identified using a meta-regulation network model. microRNAs not previously associated with IFN signalling have been identified. In contrast, only 223 known transcripts were significantly changed after imiquimod treatment, including CXCL10, and OAS1. CONCLUSION: Results suggest that IFN signalling is important in these translational models and novel miRNA may be new targets in the treatment of IFN associated skin disease.
Authors: Dimitrios Lagos; Gabriel Pollara; Stephen Henderson; Fiona Gratrix; Martin Fabani; Richard S B Milne; Frances Gotch; Chris Boshoff Journal: Nat Cell Biol Date: 2010-04-25 Impact factor: 28.824
Authors: Frederick J Sheedy; Eva Palsson-McDermott; Elizabeth J Hennessy; Cara Martin; John J O'Leary; Qingguo Ruan; Derek S Johnson; Youhai Chen; Luke A J O'Neill Journal: Nat Immunol Date: 2009-11-29 Impact factor: 25.606
Authors: Tina Ruggiero; Michele Trabucchi; Francesca De Santa; Simona Zupo; Brian D Harfe; Michael T McManus; M Geoff Rosenfeld; Paola Briata; Roberto Gherzi Journal: FASEB J Date: 2009-05-07 Impact factor: 5.191
Authors: Cristiana Guiducci; Claudio Tripodo; Mei Gong; Sabina Sangaletti; Mario P Colombo; Robert L Coffman; Franck J Barrat Journal: J Exp Med Date: 2010-11-29 Impact factor: 14.307
Authors: William R Swindell; Andrew Johnston; Steve Carbajal; Gangwen Han; Christian Wohn; Jun Lu; Xianying Xing; Rajan P Nair; John J Voorhees; James T Elder; Xiao-Jing Wang; Shigetoshi Sano; Errol P Prens; John DiGiovanni; Mark R Pittelkow; Nicole L Ward; Johann E Gudjonsson Journal: PLoS One Date: 2011-04-04 Impact factor: 3.240
Authors: Madhur P Motwani; Julia D Flint; Roel Ph De Maeyer; James N Fullerton; Andrew M Smith; Daniel Jb Marks; Derek W Gilroy Journal: J Pathol Clin Res Date: 2016-05-04
Authors: Tessa van der Kolk; Salma Assil; Rianne Rijneveld; Erica S Klaassen; Gary Feiss; Edwin Florencia; Errol P Prens; Jacobus Burggraaf; Matthijs Moerland; Robert Rissmann; Martijn B A van Doorn Journal: Clin Transl Sci Date: 2018-07-03 Impact factor: 4.689