MSK1 regulates the transcription of IL-1ra in response to TLR activation in macrophages.

The Biochemical Journal
Joanne DarraghJ Simon C Arthur

Abstract

The activity of the pro-inflammatory cytokine IL (interleukin)-1 is closely regulated in vivo via a variety of mechanisms, including both the control of IL-1 production and secretion as well as naturally occurring inhibitors of IL-1 function, such as IL-1ra (IL-1 receptor antagonist). IL-1ra is homologous with IL-1, and is able to bind but not activate the IL-1 receptor. IL-1ra can be produced by a variety of cell types, and its production is stimulated by inflammatory signals. In the present study, we show that in macrophages the TLR (Toll-like receptor)-mediated induction of IL-1ra from both its proximal and distal promoters involves the p38 and ERK1/2 (extracellular-signal-regulated kinase 1/2) MAPK (mitogen-activated protein kinase) cascades. In addition, we show that MSK1 and 2 (mitogen- and stress-activated kinase 1 and 2), kinases activated by either ERK1/2 or p38 in vivo, are required for the induction of both IL-1ra mRNA and protein. MSKs regulate IL-1ra transcription via both IL-10-dependent and -independent mechanisms in cells. Consistent with this, knockout of MSK in mice was found to result in a decrease in IL-1ra production following LPS (lipopolysaccharide) injection. MSKs therefore act as important negative regu...Continue Reading

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Citations

Sep 30, 2010·Proceedings of the National Academy of Sciences of the United States of America·Rakel CarpinteroDanielle Burger
Feb 6, 2013·Molecular and Cellular Biology·Kirsty F MacKenzieJ Simon C Arthur
Jun 1, 2010·Rheumatic Diseases Clinics of North America·Tamsin M Lindstrom, William H Robinson
Feb 15, 2012·Cellular Signalling·Johannes G BodeDieter Häussinger
Oct 6, 2011·The Biochemical Journal·Shaista NaqviJ Simon C Arthur
Jan 6, 2011·The Biochemical Journal·Hilary SmithPeter C F Cheung
May 9, 2013·Clinical Immunology : the Official Journal of the Clinical Immunology Society·Soumya D ChakravartyGeorge D Kalliolias
Apr 23, 2013·The American Journal of Pathology·Lizhi He, Alexander G Marneros
Jul 5, 2016·Frontiers in Cell and Developmental Biology·Kathleen M S E Reyskens, J Simon C Arthur
Aug 21, 2013·Nature Reviews. Immunology·J Simon C Arthur, Steven C Ley
Nov 23, 2011·Journal of Clinical and Experimental Hematopathology : JCEH·Michiaki Takagi
Dec 18, 2012·The Journal of Immunology : Official Journal of the American Association of Immunologists·Kirsty F MacKenzieJ Simon C Arthur
Aug 21, 2012·The Journal of Immunology : Official Journal of the American Association of Immunologists·Michael J PattisonJ Simon C Arthur
Nov 13, 2019·Epigenetics & Chromatin·Dandan ZongPing Chen
Aug 28, 2021·International Journal of Molecular Sciences·Naveed AkbarFaisel Khan

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