Lymphotactin gene transcription is inhibited by cyclosporine A during acute cardiac allograft rejection in mice / 中国病理生理杂志

ABSTRACT

AIM: To investigate lymphotactin (Lptn) gene transcription during acute cardiac allograft rejection and the inhibitory effect of cyclosporine A (CsA). METHODS: Graft specimens were harvested at indicated time to determine morphological changes by pathological examination. The grade of acute cardiac allograft rejection was evaluated by using modified Banff scoring system. Reverse transcription-polymerase chain reaction (RT-PCR) was used to determine the Lptn mRNA expression in cardiac grafts. NFATc1 activity of splenocytes after transplantation was assessed by enzyme-linked immunoabsordent assay (ELISA). RESULTS: Prominent splenomegaly on day 3 posttransplantation was found in C57BL/6-Balb/c group. The extent of myocardial inflammatory infiltration was scored 2.667?0.577 at day 5 and 2.333?0.577 at day 7, respectively. Splenomegaly was ameliorated by CsA treatment, and the extent of myocardial infiltrate was scored 1.000?0.000 at day 5 and 1.333?0.577 at day 7, respectively. Lymphotactin mRNA was undetectable in cardiac isografts. Lymphotactin mRNA, which was inhibited partially by CsA, was upregulated strongly in acutely rejecting cardiac allografts at day 5 and day 7. Further studies demonstrated that NFATc1 activity in splenocytes, which markedly upregulated during acute rejection, was completely inhibited by CsA. CONCLUSION: Lptn appears to be a key chemokine of lymphocyte infiltration during acute allograft rejection. Inhibition of NFATc1 activity by CsA seems to decrease Lptn expression incompletely, suggesting that there was else mechanism to regulate Lptn expression other than NFAT pathway.