[Effects of blocking the CXC chemokine receptor 3 pathway on acute rejection of islet allograft]

Zhonghua Wai Ke Za Zhi. 2007 Feb 1;45(3):210-3.
[Article in Chinese]

Abstract

Objective: To identify the effect of PNA CXCR3 on acute rejection of islet allograft.

Methods: The mice islet transplant models were used. The mice were divided into three groups including saline group, PNA CXCR3 group and mismatch PNA group. In vitro the proliferation capability of T cell was assessed by proliferative responses. RT-PCR and western blot were used to detect the expression of mRNA and protein. Flow cytometry was applied to determine the expression level of CXCR3 in spleen CD3(+) T cells.

Results: Compared with saline [(6.72 +/- 1.48) d] and PNA mismatch-treated recipients [(6.54 +/- 0.86) d], PNA CXCR3-treated recipients demonstrated statistically significant prolongation [(9.70 +/- 1.57) d] in functional allograft survival. The CXCR3 mRNA expression level of PNA CXCR3 group (1.06 +/- 0.07) was significantly down-regulated compared with saline (1.98 +/- 0.22) and PNA mismatch (1.87 +/- 0.10) group at the 7th day after transplant. The date showed that CXCR3 protein and lymphocytes proliferation capability was significantly down-regulated in PNA CXCR3 group compared with saline and PNA mismatch group (P<0.01).

Conclusions: The present study indicates that PNA CXCR3 can inhibit T cell activating and prolonging the survival time of islet allograft and has a substantial therapeutic effect on inhibiting acute allograft rejection.

Publication types

  • English Abstract

MeSH terms

  • Animals
  • Blotting, Western
  • Diabetes Mellitus, Experimental / surgery
  • Graft Rejection / genetics
  • Graft Rejection / physiopathology*
  • Graft Survival / drug effects
  • Graft Survival / genetics
  • Graft Survival / physiology
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Oligonucleotides, Antisense / administration & dosage
  • Oligonucleotides, Antisense / genetics
  • Pancreas Transplantation / methods*
  • Peptide Nucleic Acids / administration & dosage
  • Peptide Nucleic Acids / genetics
  • Random Allocation
  • Receptors, CXCR3 / genetics
  • Receptors, CXCR3 / metabolism
  • Receptors, CXCR3 / physiology*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Signal Transduction / drug effects
  • Signal Transduction / genetics
  • Signal Transduction / physiology*
  • Transplantation, Homologous

Substances

  • Oligonucleotides, Antisense
  • Peptide Nucleic Acids
  • Receptors, CXCR3