Microarray analyses demonstrate the involvement of type i interferons in psoriasiform pathology development in D6-deficient mice

Baldwin, H.M., Pallas, K., King, V., Jamieson, T., McKimmie, C.S., Nibbs, R.J.B. , Carballido, J.M., Jaritz, M., Rot, A. and Graham, G.J. (2013) Microarray analyses demonstrate the involvement of type i interferons in psoriasiform pathology development in D6-deficient mice. Journal of Biological Chemistry, 288(51), pp. 36473-36483. (doi: 10.1074/jbc.M113.491563)

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Abstract

The inflammatory response is normally limited by mechanisms regulating its resolution. In the absence of resolution, inflammatory pathologies can emerge, resulting in substantial morbidity and mortality. We have been studying the D6 chemokine scavenging receptor, which played an indispensable role in the resolution phase of inflammatory responses and does so by facilitating removal of inflammatory CC chemokines. In D6-deficient mice, otherwise innocuous cutaneous inflammatory stimuli induce a grossly exaggerated inflammatory response that bears many similarities to human psoriasis. In the present study, we have used transcriptomic approaches to define the molecular make up of this response. The data presented highlight potential roles for a number of cytokines in initiating and maintaining the psoriasis-like pathology. Most compellingly, we provide data indicating a key role for the type I interferon pathway in the emergence of this pathology. Neutralizing antibodies to type I interferons are able to ameliorate the psoriasis-like pathology, confirming a role in its development. Comparison of transcriptional data generated from this mouse model with equivalent data obtained from human psoriasis further demonstrates the strong similarities between the experimental and clinical systems. As such, the transcriptional data obtained in this preclinical model provide insights into the cytokine network active in exaggerated inflammatory responses and offer an excellent tool to evaluate the efficacy of compounds designed to therapeutically interfere with inflammatory processes.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Baldwin, Dr Helen and King, Dr Vicky and Pallas, Mr Kenny and Nibbs, Professor Rob and Jamieson, Mr Thomas and McKimmie, Dr Clive and Graham, Professor Gerard
Authors: Baldwin, H.M., Pallas, K., King, V., Jamieson, T., McKimmie, C.S., Nibbs, R.J.B., Carballido, J.M., Jaritz, M., Rot, A., and Graham, G.J.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cancer Sciences
Journal Name:Journal of Biological Chemistry
Journal Abbr.:J Biol Chem.
Publisher:American Society for Biochemistry and Molecular Biology, Inc.
ISSN:0021-9258
ISSN (Online):1083-351X
Copyright Holders:Copyright © 2013 The Authors
First Published:First published in Journal of Biological Chemistry 288(51):36473-36483
Publisher Policy:Reproduced under a Creative Commons License

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