FTY720 impairs necrosis development after ischemia-reperfusion injury.
Ischemia-reperfusion (IR) injury is a common early feature that contributes to graft damage by impairing resident cell function. Our previous results showed that IR injury impaired renal function, by causing extensive tubular necrosis and increasing MHC class II and ICAM-1 molecule expression by mesangial cells (MC). MCs are likely candidates to come into close contact with immune cells such as monocytes or lymphocytes. It has been suggested that under inflammatory circumstances, there is increased MC expression of MHC class II, of adhesion molecules (such as ICAM-1), of cytokines receptors, and of molecules associated with cellular death (apoptosis). The immunosuppressive properties of FTY720 have been shown in clinical and experimental situations. It has also been shown to be protective against IR injury in rats. We sought to evaluate the role of FTY720 in a murine IR model by measuring renal function, tubular necrosis, and surface molecule expression by cultured mesangial cells. Intravenous administration of FTY720 (1 mg/kg) immediately before IR induction did not improve the short-term (24 hours) outcome of renal function or reduced MHC class II and ICAM-1 surface molecule expression. However, there was a decreased percentage of tubular necrosis in mice treated with FTY720 (51.3% +/- 1.6%) compared with vehicle-treated mice (66% +/- 5.5%). These results suggest a protective role of FTY720 in an IR injury model. More studies are required to identify the mechanisms involved in the protective activity of FTY720 in the IR injury model.
Oliveira
C M S
CM
Nephrology Division, Department of Medicine, Paulista Medical School, UNIFESP, Sao Paulo, Brazil.
Borra
R C
RC
Franco
M
M
Schor
N
N
Silva
H T
HT
Pestana
J O M
JO
Bueno
V
V
D000704:Analysis of Variance; D000818:Animals; D003404:Creatinine / Q000097:blood; D004195:Disease Models, Animal; D000068876:Fingolimod Hydrochloride; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D008099:Liver / Q000098:blood supply* / Q000187:drug effects / Q000473:pathology; D051379:Mice; D009336:Necrosis; D011409:Propylene Glycols / Q000627:therapeutic use*; D015427:Reperfusion Injury / Q000517:prevention & control*; D013110:Sphingosine / Q000031:analogs & derivatives; D014508:Urea / Q000652:urine
D007166:Immunosuppressive Agents; D011409:Propylene Glycols; D014508:Urea; D003404:Creatinine; D000068876:Fingolimod Hydrochloride; D013110:Sphingosine