Clearance of apoptotic cells: TGF-beta in the balance between inflammation and fibrosis.
Transforming growth factor-beta (TGF-beta) has been considered an anti-inflammatory cytokine responsible for the bland removal of apoptotic cells. What is less established is the extent of secretion of this cytokine during the clearance of opsonized apoptotic cells via Fcgamma-mediated uptake. To date both decreased (favoring predominance of inflammation) and increased (favoring resolution of inflammation but potentially pro-fibrotic) responses have been demonstrated. IN an in vitro model of autoantibody-induced cardiac injury, we herein demonstrate that macrophages cocultured with apoptotic human fetal cardiocytes bound by anti-SSA/Ro antibodies secrete increased levels of TGF-beta. Prolonged secretion of this cytokine may contribute to the exuberant scarring seen in congenital heart block associated with maternal autoantibodies reactive with SSA/Rho and SSB/La antigens.
Clancy
Robert M
RM
Buyon
Jill P
JP
D000974:Antibodies, Antinuclear / Q000276:immunology; D017209:Apoptosis / Q000276:immunology*; D018920:Coculture Techniques; D005355:Fibrosis; D006327:Heart Block / Q000151:congenital; D006801:Humans; D007249:Inflammation; D008264:Macrophages / Q000276:immunology*; D009206:Myocardium / Q000166:cytology*; D016212:Transforming Growth Factor beta / Q000378:metabolism*
D000974:Antibodies, Antinuclear; C035356:SS-A antibodies; D016212:Transforming Growth Factor beta