Targeting interleukin-1 signaling in chronic inflammation: focus on P2X(7) receptor and Pannexin-1.
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.
Pelegrin
Pablo
P
Faculty of Life Science, University of Manchester, Manchester, England, U.K. pelegrin@manchester.ac.uk
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D002908:Chronic Disease; D017630:Connexins / Q000502:physiology*; D005786:Gene Expression Regulation; D007249:Inflammation / Q000378:metabolism*; D007375:Interleukin-1 / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D009419:Nerve Tissue Proteins / Q000502:physiology*; D058919:Purinergic P2 Receptor Antagonists; D017472:Receptors, Interleukin-1 / Q000819:agonists; D018048:Receptors, Purinergic P2 / Q000502:physiology*; D058486:Receptors, Purinergic P2X7; D015398:Signal Transduction
D000893:Anti-Inflammatory Agents; D017630:Connexins; D007375:Interleukin-1; D009419:Nerve Tissue Proteins; C546469:P2rx7 protein, mouse; C503631:Panx1 protein, mouse; D058919:Purinergic P2 Receptor Antagonists; D017472:Receptors, Interleukin-1; D018048:Receptors, Purinergic P2; D058486:Receptors, Purinergic P2X7