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    Drug News Perspect. 2008 Oct;21(8):424-33.

    Targeting interleukin-1 signaling in chronic inflammation: focus on P2X(7) receptor and Pannexin-1.

    Source

    Faculty of Life Science, University of Manchester, Manchester, England, U.K. pelegrin@manchester.ac.uk

    Abstract

    Innate immunity is the most ancient system to protect multicellular hosts from infections. In vertebrates it is regulated by an extensive and complex network of cytokines that orchestrate inflammation, a response of the body to invasion by infectious agents or to tissue damage. One of the key cytokines that initiates inflammation is interleukin (IL)-1 and aberrant production of IL-1, due to a failure in any of its regulatory steps, leads to chronic inflammatory diseases. The discovery of new proteins regulating IL-1 processing and release opens an exciting field for the design of novel antiinflammatory drugs. Among those are the purinergic ATP-gated P2X(7) receptor (P2X(7)R) and its downstream signaling molecule Pannexin-1 (Panx-1), both involved in the control of the activation and the release of mature IL-1alpha, IL-1beta and IL-18. This review will focus on the potential targets for each step in the IL-1 signaling process, from gene expression through activation of IL-1 receptor by released cytokines, with particular attention paid to the involvement of P2X(7)R and Panx-1.

    Copyright 2008 Prous Science, S.A.U. or its licensors. All rights reserved.

    PMID:
    19034348
    [PubMed - indexed for MEDLINE]

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