Heme oxygenase-1, a protective gene that prevents the rejection of transplanted organs.
Endothelial cells (EC) play a pivotal role in regulating inflammatory reactions such as those involved in the rejection of transplanted organs. This occurs through the expression of a series of pro- and anti-inflammatory genes that are associated with the activation of these cells. Presumably, the expression of pro-inflammatory genes promotes events that lead to graft rejection, while expression of anti-inflammatory (protective) genes suppresses those events and thus contributes in sustaining graft survival. Understanding how the expression of these genes is regulated and their mechanism of action are important issues for the development of new therapeutic strategies to suppress graft rejection. We have studied this phenomenon using experimental models of transplantation in rats. We discuss here data that supports the concept that grafts can express anti-inflammatory (protective) genes that mitigate inflammatory reactions leading to graft rejection. The data reviewed focus on the role of one of such genes, the stress responsive gene heme oxygenase-1, and of its byproduct carbon monoxide, which can suppress graft rejection and lead to long-term graft survival.
Soares
M P
MP
Beth Israel Deaconess Medical Center, Department of Surgery, Harvard Medical School, Boston, MA 02215, USA. msoares@caregroup.harvard.edu
Brouard
S
S
Smith
R N
RN
Bach
F H
FH
D000818:Animals; D017209:Apoptosis; D002248:Carbon Monoxide; D004730:Endothelium, Vascular / Q000166:cytology / Q000276:immunology; D006084:Graft Rejection / Q000201:enzymology* / Q000276:immunology; D006419:Heme Oxygenase (Decyclizing) / Q000235:genetics / Q000276:immunology*; D051547:Heme Oxygenase-1; D006801:Humans; D008565:Membrane Proteins
D008565:Membrane Proteins; D002248:Carbon Monoxide; C496541:HMOX1 protein, human; D006419:Heme Oxygenase (Decyclizing); D051547:Heme Oxygenase-1