title: Genome-wide transcriptional profiling of skin and dorsal root ganglia after ultraviolet-B-induced inflammation.
abstract: Ultraviolet-B (UVB)-induced inflammation produces a dose-dependent mechanical and thermal hyperalgesia in both humans and rats, most likely via inflammatory mediators acting at the site of injury. Previous work has shown that the gene expression of cytokines and chemokines is positively correlated between species and that these factors can contribute to UVB-induced pain. In order to investigate other potential pain mediators in this model we used RNA-seq to perform genome-wide transcriptional profiling in both human and rat skin at the peak of hyperalgesia. In addition we have also measured transcriptional changes in the L4 and L5 DRG of the rat model. Our data show that UVB irradiation produces a large number of transcriptional changes in the skin: 2186 and 3888 genes are significantly dysregulated in human and rat skin, respectively. The most highly up-regulated genes in human skin feature those encoding cytokines (IL6 and IL24), chemokines (CCL3, CCL20, CXCL1, CXCL2, CXCL3 and CXCL5), the prostanoid synthesising enzyme COX-2 and members of the keratin gene family. Overall there was a strong positive and significant correlation in gene expression between the human and rat (R = 0.8022). In contrast to the skin, only 39 genes were significantly dysregulated in the rat L4 and L5 DRGs, the majority of which had small fold change values. Amongst the most up-regulated genes in DRG were REG3B, CCL2 and VGF. Overall, our data shows that numerous genes were up-regulated in UVB irradiated skin at the peak of hyperalgesia in both human and rats. Many of the top up-regulated genes were cytokines and chemokines, highlighting again their potential as pain mediators. However many other genes were also up-regulated and might play a role in UVB-induced hyperalgesia. In addition, the strong gene expression correlation between species re-emphasises the value of the UVB model as translational tool to study inflammatory pain.
authors.affiliation: Nuffield Department of Clinical Neurosciences, University of Oxford, John Radcliffe Hospital, Oxford, United Kingdom.
authors.forename: John M
authors.initials: JM
authors.lastname: Dawes
authors.affiliation: Wolfson Centre for Age-Related Disease, King's College London, London, United Kingdom.
authors.forename: Ana
authors.initials: A
authors.lastname: Antunes-Martins
authors.affiliation: Department of Structural and Molecular Biology, University College London, London, United Kingdom.
authors.forename: James R
authors.initials: JR
authors.lastname: Perkins
authors.affiliation: Wolfson Centre for Age-Related Disease, King's College London, London, United Kingdom.
authors.forename: Kathryn J
authors.initials: KJ
authors.lastname: Paterson
authors.affiliation: Institute of Clinical Pharmacology, Pharmazentrum Frankfurt/Zentrum fuer Arzneimittelforschung, -Entwicklung und -Sicherheit (ZAFES), University Hospital, Goethe-University, Frankfurt am Main, Germany.
authors.forename: Marco
authors.initials: M
authors.lastname: Sisignano
authors.affiliation: Boehringer Ingelheim Pharma GmbH & Co. KG, Target Discovery Research Germany, Biberach an der Riß, Germany.
authors.forename: Ramona
authors.initials: R
authors.lastname: Schmid
authors.affiliation: Boehringer Ingelheim Pharma GmbH & Co. KG, Target Discovery Research Germany, Biberach an der Riß, Germany.
authors.forename: Werner
authors.initials: W
authors.lastname: Rust
authors.affiliation: Boehringer Ingelheim Pharma GmbH & Co. KG, Target Discovery Research Germany, Biberach an der Riß, Germany.
authors.forename: Tobias
authors.initials: T
authors.lastname: Hildebrandt
authors.affiliation: Institute of Clinical Pharmacology, Pharmazentrum Frankfurt/Zentrum fuer Arzneimittelforschung, -Entwicklung und -Sicherheit (ZAFES), University Hospital, Goethe-University, Frankfurt am Main, Germany.
authors.forename: Gerd
authors.initials: G
authors.lastname: Geisslinger
authors.affiliation: Department of Structural and Molecular Biology, University College London, London, United Kingdom.
authors.forename: Christine
authors.initials: C
authors.lastname: Orengo
authors.affiliation: Nuffield Department of Clinical Neurosciences, University of Oxford, John Radcliffe Hospital, Oxford, United Kingdom.
authors.forename: David L
authors.initials: DL
authors.lastname: Bennett
authors.affiliation: Wolfson Centre for Age-Related Disease, King's College London, London, United Kingdom.
authors.forename: Stephen B
authors.initials: SB
authors.lastname: McMahon
mesh_terms: D000818:Animals; D000951:Antigens, Neoplasm / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000378:metabolism; D018932:Chemokine CCL2 / Q000378:metabolism; D005727:Ganglia, Spinal / Q000378:metabolism* / Q000473:pathology / Q000528:radiation effects; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000528:radiation effects; D016678:Genome / Q000235:genetics*; D006801:Humans; D007249:Inflammation / Q000235:genetics* / Q000473:pathology*; D037181:Lectins, C-Type / Q000378:metabolism; D008297:Male; D008954:Models, Biological; D000073718:Pancreatitis-Associated Proteins; D017208:Rats, Wistar; D012015:Reference Standards; D015203:Reproducibility of Results; D017423:Sequence Analysis, RNA; D012867:Skin / Q000378:metabolism* / Q000473:pathology / Q000528:radiation effects; D014158:Transcription, Genetic / Q000528:radiation effects; D014466:Ultraviolet Rays; D015854:Up-Regulation / Q000235:genetics / Q000528:radiation effects
chemical_list: D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D018932:Chemokine CCL2; D037181:Lectins, C-Type; D000073718:Pancreatitis-Associated Proteins; C000612141:REG3A protein, human
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