Thymosin β4-sulfoxide attenuates inflammatory cell infiltration and promotes cardiac wound healing

Nicola Smart, Karina N Dubé, Sveva Bollini, Hayley G Evans, Leonie S Taams, Rebecca Richardson, Mathieu Lévesque, Paul Martin, Kevin Mills, Johannes Riegler, Anthony N Price, Mark F Lythgoe, Paul R Riley

Research output: Contribution to journalArticle (Academic Journal)

44 Citations (Scopus)

Abstract

The downstream consequences of inflammation in the adult mammalian heart are formation of a non-functional scar, pathological remodelling and heart failure. In zebrafish, hydrogen peroxide released from a wound is the initial instructive chemotactic cue for the infiltration of inflammatory cells, however, the identity of a subsequent resolution signal(s), to attenuate chronic inflammation, remains unknown. Here we reveal that thymosin β4-sulfoxide lies downstream of hydrogen peroxide in the wounded fish and triggers depletion of inflammatory macrophages at the injury site. This function is conserved in the mouse and observed after cardiac injury, where it promotes wound healing and reduced scarring. In human T-cell/CD14+ monocyte co-cultures, thymosin β4-sulfoxide inhibits interferon-γ, and increases monocyte dispersal and cell death, likely by stimulating superoxide production. Thus, thymosin β4-sulfoxide is a putative target for therapeutic modulation of the immune response, resolution of fibrosis and cardiac repair.
Original languageEnglish
Pages (from-to)2081
JournalNature Communications
Volume4
DOIs
Publication statusPublished - 2013

Keywords

  • Amino Acid Sequence
  • Animals
  • Cell Adhesion
  • Cell Death
  • Cell Movement
  • Humans
  • Hydrogen Peroxide
  • Inflammation
  • Leukocytes
  • Macrophages
  • Mice
  • Mice, Inbred C57BL
  • Molecular Sequence Data
  • Monocytes
  • Myocardial Infarction
  • Myocardium
  • Reactive Oxygen Species
  • Thymosin
  • Wound Healing
  • Zebrafish

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    Smart, N., Dubé, K. N., Bollini, S., Evans, H. G., Taams, L. S., Richardson, R., Lévesque, M., Martin, P., Mills, K., Riegler, J., Price, A. N., Lythgoe, M. F., & Riley, P. R. (2013). Thymosin β4-sulfoxide attenuates inflammatory cell infiltration and promotes cardiac wound healing. Nature Communications, 4, 2081. https://doi.org/10.1038/ncomms3081