David Brough

Summary

Affiliation: University of Manchester
Country: UK

Publications

  1. Strangward P, Haley M, Albornoz M, Barrington J, Shaw T, Dookie R, et al. Targeting the IL33-NLRP3 axis improves therapy for experimental cerebral malaria. Proc Natl Acad Sci U S A. 2018;115:7404-7409 pubmed publisher
    ..Our results therefore demonstrate that manipulation of the IL33-NLRP3 axis may be an effective therapy to suppress neuroinflammation and improve the efficacy of antimalarial drug treatment of CM. ..
  2. Denes A, Coutts G, Lénárt N, Cruickshank S, Pelegrin P, Skinner J, et al. AIM2 and NLRC4 inflammasomes contribute with ASC to acute brain injury independently of NLRP3. Proc Natl Acad Sci U S A. 2015;112:4050-5 pubmed publisher
    ..These discoveries identify the NLRC4 and AIM2 inflammasomes as potential therapeutic targets for stroke and provide new insights into how the inflammatory response is regulated after an acute injury to the brain. ..
  3. Green J, Yu S, Martín Sánchez F, Pelegrin P, Lopez Castejon G, Lawrence C, et al. Chloride regulates dynamic NLRP3-dependent ASC oligomerization and inflammasome priming. Proc Natl Acad Sci U S A. 2018;: pubmed publisher
    ..Our investigation delivers mechanistic understanding into inflammasome activation and the regulation of inflammatory responses. ..
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    Brough D, Rothwell N. Caspase-1-dependent processing of pro-interleukin-1beta is cytosolic and precedes cell death. J Cell Sci. 2007;120:772-81 pubmed
    ..We propose that, in macrophages, ATP-induced interleukin-1beta processing occurs in the cytosol by a mechanism that resembles pyroptosis. ..
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    Brough D, Sim Y, Thorn P, Irvine R. The structural integrity of the endoplasmic reticulum, and its possible regulation by inositol 1,3,4,5-tetrakisphosphate. Cell Calcium. 2005;38:153-9 pubmed
    ..However, we were subsequently unable to detect by FRAP any significant effect of Ins(1,3,4,5)P(4) on ER integrity. ..
  6. Rivers Auty J, Daniels M, Colliver I, Robertson D, Brough D. Redefining the ancestral origins of the interleukin-1 superfamily. Nat Commun. 2018;9:1156 pubmed publisher
    ..IL-1α formed from the duplication of IL-1β, and moonlighting functions of pro-IL-1α acted as divergent selection pressures for the observed sequence dissimilarity. ..
  7. Redondo Castro E, Faust D, Fox S, Baldwin A, Osborne S, Haley M, et al. Development of a characterised tool kit for the interrogation of NLRP3 inflammasome-dependent responses. Sci Rep. 2018;8:5667 pubmed publisher
  8. Edye M, Brough D, Allan S. Acid-dependent Interleukin-1 (IL-1) Cleavage Limits Available Pro-IL-1β for Caspase-1 Cleavage. J Biol Chem. 2015;290:25374-81 pubmed publisher
    ..Therefore formation of the 20-kDa form of IL-1β may prevent the generation of mature bioactive IL-1β and thus may limit inflammation. ..
  9. Daniels M, Brough D. Unconventional Pathways of Secretion Contribute to Inflammation. Int J Mol Sci. 2017;18: pubmed publisher
    ..In this review we discuss the current understanding of the unconventional secretion of these proteins and highlight future areas of research such as the role of nuclear localisation. ..

More Information

Publications16

  1. Haley M, Brough D, Quintin J, Allan S. Microglial Priming as Trained Immunity in the Brain. Neuroscience. 2017;: pubmed publisher
    ..Although such changes may be beneficial in peripheral infectious disease, in the context of microglial priming they may drive increased microglia reactivity that is damaging in diseases of brain aging. ..
  2. Brough D, Pelegrin P, Rothwell N. Pannexin-1-dependent caspase-1 activation and secretion of IL-1beta is regulated by zinc. Eur J Immunol. 2009;39:352-8 pubmed publisher
    ..These data provide new insights into the mechanisms of caspase-1 activation and how zinc metabolism contributes to inflammatory mechanisms. ..
  3. Diamond C, Bagnall J, Spiller D, White M, Mortellaro A, Paszek P, et al. Investigating IL-1? Secretion Using Real-Time Single-Cell Imaging. Methods Mol Biol. 2016;1417:75-88 pubmed publisher
  4. Diamond C, Leong K, Vacca M, Rivers Auty J, Brough D, Mortellaro A. Salmonella typhimurium-induced IL-1 release from primary human monocytes requires NLRP3 and can occur in the absence of pyroptosis. Sci Rep. 2017;7:6861 pubmed publisher
    ..This insight into the mechanisms involved in IL-1 release from primary human monocytes highlights major differences between immune cell types, and the defences they employ during bacterial infection. ..
  5. Brough D, Pelegrin P, Nickel W. An emerging case for membrane pore formation as a common mechanism for the unconventional secretion of FGF2 and IL-1?. J Cell Sci. 2017;130:3197-3202 pubmed publisher
    ..In this Opinion article, we discuss the unconventional mechanisms of FGF2 and IL-1? release with a particular emphasis on recent discoveries suggesting the importance of pore formation on the plasma membrane. ..
  6. Baldwin A, Rivers Auty J, Daniels M, White C, Schwalbe C, Schilling T, et al. Boron-Based Inhibitors of the NLRP3 Inflammasome. Cell Chem Biol. 2017;24:1321-1335.e5 pubmed publisher
    ..The NBC compounds represent useful tools to dissect NLRP3 function, and may lead to oxazaborine ring-containing therapeutics. ..
  7. Daniels M, Adamson A, Humphreys N, Brough D. CRISPR/Cas9 mediated mutation of mouse IL-1? nuclear localisation sequence abolishes expression. Sci Rep. 2017;7:17077 pubmed publisher
    ..Our results serve as a cautionary note that CRISPR -mediated genome editing without full knowledge of genomic context can result in unexpected, yet potentially informative observations. ..