J Korean Soc Transplant.  2002 Jun;16(1):22-29.

The Regulation of Cytokine and Chemokine Expressions in Skin Xenograft by Aminoguanidine

• Kim D
• Kim JY
• Ahn C
• Yang MG
• Lee EM
• Yoon HY
• Song M
• Park CG
• Ha J
• Kim JG
• Shin KS
• Kim SJ
• Lee JS

Abstract

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 mg/kg). 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-1beta, IL-2, IL-6, IL-12, IFN-gamma in AMG treated graft significantly decreased (P<0.01) whereas IL- 10, TNF-alpha and TGF-beta1 were not changed or enhanced. Additionally, the expression of CC-chemokines such as RANTES and MIP-1alpha 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.

Keyword

Xenotransplantation; Nitric oxide; iNOS; Cytokines; Chemokines

MeSH Terms

Allografts
Animals
Chemokine CCL3
Chemokine CCL5
Chemokines
Cytokines
Graft Rejection
Graft Survival
Heterografts*
Interleukin-12
Interleukin-2
Interleukin-6
Mice
Neutrophils
Nitric Oxide
Rats
RNA, Messenger
Skin*
Tail
Transforming Growth Factor beta1
Transplantation, Heterologous
Transplants
Tumor Necrosis Factor-alpha
Chemokine CCL3
Chemokine CCL5
Chemokines
Cytokines
Interleukin-12
Interleukin-2
Interleukin-6
Nitric Oxide
RNA, Messenger
Transforming Growth Factor beta1
Tumor Necrosis Factor-alpha