Thymosin beta4-sulfoxide attenuates inflammatory cell infiltration and promotes cardiac wound healing
- Authors
- Evans, M.A., Smart, N., Dube, K.N., Bollini, S., Clark, J.E., Evans, H.G., Taams, L.S., Richardson, R., Levesque, M., Martin, P., Mills, K., Riegler, J., Price, A.N., Lythgoe, M.F., and Riley, P.R.
- ID
- ZDB-PUB-130710-126
- Date
- 2013
- Source
- Nature communications 4: 2081 (Journal)
- Registered Authors
- Evans, Mark, Lévesque, Mathieu, Martin, Paul, Richardson, Rebecca
- Keywords
- Cardiovascular diseases, Inflammation, Monocytes and macrophages, Signal transduction
- MeSH Terms
-
- Mice, Inbred C57BL
- Zebrafish
- Mice
- Cell Movement/drug effects*
- Monocytes/drug effects
- Monocytes/pathology
- Cell Adhesion/drug effects
- Animals
- Macrophages/drug effects
- Macrophages/metabolism
- Reactive Oxygen Species/metabolism
- Wound Healing/drug effects*
- Humans
- Molecular Sequence Data
- Inflammation/pathology*
- Myocardial Infarction/pathology
- Hydrogen Peroxide/pharmacology
- Amino Acid Sequence
- Leukocytes/drug effects
- Cell Death/drug effects
- Thymosin/chemistry
- Thymosin/pharmacology*
- Myocardium/pathology*
- PubMed
- 23820300 Full text @ Nat. Commun.
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.