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A Zebrafish Compound Screen Reveals Modulation of Neutrophil Reverse Migration as an Anti-Inflammatory Mechanism

Research output: Contribution to journalArticle

  • Anne L. Robertson
  • Geoffrey R. Holmes
  • Aleksandra N. Bojarczuk
  • Joseph Burgon
  • Catherine A. Loynes
  • Myriam Chimen
  • Amy K. Sawtell
  • Bashar Hamza
  • Joseph Willson
  • Sean R. Anderson
  • Mark C. Coles
  • Stuart N. Farrow
  • Roberto Solari
  • Simon Jones
  • Lynne R. Prince
  • Daniel Irimia
  • G. Ed Rainger
  • Visakan Kadirkamanathan
  • Stephen A. Renshaw

Related Edinburgh Organisations

Original languageEnglish
Article number225ra29
Number of pages10
JournalScience Translational Medicine
Volume6
Issue number225
DOIs
Publication statusPublished - 26 Feb 2014

Abstract

Diseases of failed inflammation resolution are common and largely incurable. Therapeutic induction of inflammation resolution is an attractive strategy to bring about healing without increasing susceptibility to infection. However, therapeutic targeting of inflammation resolution has been hampered by a lack of understanding of the underlying molecular controls. To address this drug development challenge, we developed an in vivo screen for proresolution therapeutics in a transgenic zebrafish model. Inflammation induced by sterile tissue injury was assessed for accelerated resolution in the presence of a library of known compounds. Of the molecules with proresolution activity, tanshinone IIA, derived from a Chinese medicinal herb, potently induced inflammation resolution in vivo both by induction of neutrophil apoptosis and by promoting reverse migration of neutrophils. Tanshinone IIA blocked proinflammatory signals in vivo, and its effects are conserved in human neutrophils, supporting a potential role in treating human inflammation and providing compelling evidence of the translational potential of this screening strategy.

    Research areas

  • NF-KAPPA-B, INFLAMMATORY CELL APOPTOSIS, TRANSGENIC ZEBRAFISH, ENDOTHELIAL-CELLS, KINASE INHIBITOR, GENE-EXPRESSION, RAW-264.7 CELLS, IN-VIVO, RESOLUTION, ADHESION

ID: 17163997