Purpose: Previous reports demonstrated that nitric oxide (NO) plays immuno-regulatory role in immune responses including allograft rejection response. However, its possible role in xenograft rejection has not been examined. The purpose of
this
study is to elucidate possible immunoregulatory role of NO in skin xenograft rejection by determining the expressions of chemokines and cytokines in the presence or absence of iNOS inhibitors.
Methods: C57BL/6J mice were grafted with Lewis rat tail skin. The mice were injected intraperitoneally with potent inhibitor of iNOS, aminoguanidine (AMG, 200 ㎎/㎏). Graft survival was monitored and cytokine and chemokine mRNA expressions
were
measured by real-time RT-PCR in context with iNOS expression on day 3, 5, 7 and 9. These data were compared with those of control mice (saline injected).
Results: Compared with the control mice, the AMG treated mice showed delayed xenograft rejection by approximately 3 days (8.9±0.7 days vs 11.7±1.2 days). Infiltrations of CD11b+, MOMA-2+ cells and neutrophils were
significantly reduced but not CD4+ and CD8+ cells in AMG treated graft. The expression of cytokines such as IL-1β, IL-2, IL-6, IL-12, IFN-γ in AMG treated graft significantly decreased (P＜0.01) whereas IL- 10, TNF-α and
TGF-β1
were not changed or enhanced. Additionally, the expression of CC-chemokines such as RANTES and MIP-1α significantly reduced (P＜0.01) whereas CXC-chemokines such as IP-10 and MIG did not change.
Conclusion: These data imply that NO suppression by iNOS inhibitor may prolong rat to mouse skin xenograft survival through a selective inhibition of pro-inflammatory cytokines and chemokines. The possible role of NO in transplant
rejection
can
be, therefore, extended to regulation of cytokine and chemokine expressions.
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