Thymosin β4-sulfoxide Attenuates Inflammatory Cell Infiltration and Promotes Cardiac Wound Healing

Nat Commun. 2013;4:2081. doi: 10.1038/ncomms3081.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

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

Substances

  • Reactive Oxygen Species
  • thymosin beta(4) sulfoxide
  • thymosin beta(4)
  • Thymosin
  • Hydrogen Peroxide