Is the Fas/Fas-L pathway a promising target for treating inflammatory heart disease?
The elucidation of the intricate molecular network of costimulus and regulatory pathways of the immune system led to the design of molecular therapies that specifically inactivate some cellular responses and ameliorate some autoimmune and inflammatory diseases. This innovative concept opens a new class of therapies, and one of the central components that could be targeted in future molecular therapies is the Fas-based pathway. Both soluble and membrane-bound Fas and Fas-L molecules exert a wide range of proinflammatory functions through the secretion of cytokines and chemokines, cellular chemotaxis, transcriptional regulation, cellular death, and others. Accordingly, many chronic inflammatory diseases, including myocarditis, are attenuated in mice lacking either molecule. Although it is tempting to speculate that the Fas/Fas-L pathway could be targeted for in vivo myocarditis therapy, the plurality of Fas/Fas-L functions can be an obstacle, leading to important side effects. In this review, we suggest that the injection of nonagonistic antibodies raised against the Fas molecule or the inactivation of downstream Fas-1,4,5-inositol triphosphate cascade are possible targets for myocarditis treatment.
Henriques-Pons
Andréa
A
Laboratório de Biologia Celular, Fundação Oswaldo Cruz, Instituto Oswaldo Cruz, Rio de Janeiro, RJ, Brazil. andreah@ioc.fiocruz.br
de Oliveira
Gabriel Melo
GM
D000818:Animals; D000906:Antibodies / Q000627:therapeutic use; D017209:Apoptosis / Q000502:physiology; D053222:Fas Ligand Protein / Q000276:immunology / Q000502:physiology*; D009205:Myocarditis / Q000276:immunology / Q000378:metabolism / Q000628:therapy*; D019014:fas Receptor / Q000502:physiology*
D000906:Antibodies; D053222:Fas Ligand Protein; D019014:fas Receptor