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Thymosin β4-sulfoxide attenuates inflammatory cell infiltration and promotes cardiac wound healing.
- Source :
-
Nature communications [Nat Commun] 2013; Vol. 4, pp. 2081. - Publication Year :
- 2013
-
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.
- Subjects :
- Amino Acid Sequence
Animals
Cell Adhesion drug effects
Cell Death drug effects
Humans
Hydrogen Peroxide pharmacology
Leukocytes drug effects
Macrophages drug effects
Macrophages metabolism
Mice
Mice, Inbred C57BL
Molecular Sequence Data
Monocytes drug effects
Monocytes pathology
Myocardial Infarction pathology
Reactive Oxygen Species metabolism
Thymosin chemistry
Zebrafish
Cell Movement drug effects
Inflammation pathology
Myocardium pathology
Thymosin pharmacology
Wound Healing drug effects
Subjects
Details
- Language :
- English
- ISSN :
- 2041-1723
- Volume :
- 4
- Database :
- MEDLINE
- Journal :
- Nature communications
- Publication Type :
- Academic Journal
- Accession number :
- 23820300
- Full Text :
- https://doi.org/10.1038/ncomms3081