| Targeting inflammation by modulating the Jun/AP-1 pathway. | |
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MedLine Citation:
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PMID: 21339212 Owner: NLM Status: In-Data-Review |
Abstract/OtherAbstract:
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Inflammation is a physiological response of the body to tissue injury, pathogen invasion and irritants. In the course of inflammation, immune cells of the innate and/or adaptive immune system are activated and recruited to the site of inflammation. Attraction and activation of immune cells is regulated by a variety of different cytokines and chemokines, which are predominantly regulated by transcription factors such as AP-1, NF-κB, NFATs and STATs. The evidence that Jun/AP-1 proteins control inflammation in the skin is summarised in this article. Genetic mouse models have demonstrated that a loss of Jun/AP-1 expression in epidermal cells controls cytokine expression through transcriptional and post-transcriptional pathways. The absence of JunB in epithelial K5-expressing tissues leads to a multiorgan disease, which is characterised by increased levels of granulocyte colony-stimulating factor and interleukin 6. Deletion of both JunB and c-Jun, in a constitutive or inducible manner, leads to perinatal death of newborn pups and to a psoriasis-like disease in adults, in which tumour necrosis factor α and the TIMP-3/TACE pathway have central roles. The loss or reduction of Jun expression in the epidermis relieves a block on cytokine expression. As a consequence, the increased levels of cytokines in mice lead to diseases reminiscent of psoriasis and systemic lupus erythematosus in human patients. New targets identified in mouse models, together with investigations on human samples, will provide important new avenues for therapeutic interventions in psoriasis and other inflammatory skin diseases. |
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Authors:
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Helia B Schonthaler; Juan Guinea-Viniegra; Erwin F Wagner |
Publication Detail:
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Type: Journal Article |
Journal Detail:
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Title: Annals of the rheumatic diseases Volume: 70 Suppl 1 ISSN: 1468-2060 ISO Abbreviation: Ann. Rheum. Dis. Publication Date: 2011 Mar |
Date Detail:
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Created Date: 2011-02-22 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0372355 Medline TA: Ann Rheum Dis Country: England |
Other Details:
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Languages: eng Pagination: i109-i112 Citation Subset: IM |
Affiliation:
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Correspondence to Dr Erwin F Wagner, Cancer Cell Biology Programme, Spanish National Cancer Research Centre (CNIO), C/Melchor Fernández Almagro 3, E-28029 Madrid, Spain; ewagner@cnio.es. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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