Changes of inducible protein-10 and regulated upon activation, normal T cell expressed and secreted protein in acute rejection of pancreas transplantation in rats. World J Gastroenterol

Department of General Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, Jiangsu Province, China.
World Journal of Gastroenterology (Impact Factor: 2.37). 08/2006; 12(26):4156-60.
Source: PubMed

ABSTRACT To investigate the role of IFN-gamma inducible protein -10 (IP-10) and regulated upon activation, normal T cell expressed and secreted (RANTES) protein in acute pancreatic allograft rejection in rats.
An experimental pancreas transplantation model was established using diabetic SD rats as the recipient, induced by applying streptozocin (STZ). Pancreas transplantation was performed with a physiologic method of portal venous and enteric drainage. Rats were divided into two groups, isograft group (group A, n = 24) and allograft group (group B, n = 24) in which either healthy SD rats or Wistar rats served as donors, respectively. Twelve diabetic or healthy SD rats were used as controls. At d 1, 4, 7, and 10 post transplantation, serum IP-10 and RANTES were assessed by ELISA and their expression in the allografts was determined by immunohistochemistry.
In group B (allograft group), the development of acute rejection was significantly correlated with increased serum concentration and tissue expression of IP-10 and RANTES, with a peak level at d 7 post transplantation. In contrast, there was no obvious change before and after transplantation in group A (isograft group).
Our study suggests a possible role of IP-10 and RANTES in acute rejection and early monitoring of chemokines may be helpful in predicting the outcome of pancreas transplantation.

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    • "PrA has been shown to promote allograft survival and reduce the infiltration of mononuclear cells in allografts [7]. Furthermore, several groups have demonstrated the importance of IP-10-mediated recruitment of T cells to allografts and identified the correlation between the development of acute rejection and the increased allograft expression of IP-10 [9], [23], [24]. Therefore, in this study we evaluated whether PrA inhibition of IP-10 expression results in reduced T cell infiltration into heart allografts. "
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    ABSTRACT: The immunosuppressant Protosappanin A (PrA), isolated from the medicinal herb, promotes cardiac allograft survival, diminishes inflammatory cell infiltration, and inhibits interferon γ-induced protein 10 kDa (IP-10) mRNA expression in rats cardiac grafts. Binding of the chemokine IP-10 to its cognate receptor, CXCR3, plays crucial roles in allograft immunity, especially by mediating the recruitment of effector T cells to allografted tissues. In this study, we attempted to determine whether PrA-mediated inhibition of IP-10 contributes to the effect of reduced T cell infiltration into cardiac allograft within a rat model. Administration of PrA (25 mg/kg daily) via oral gavage following heart transplantation significantly reduced the increase of IP-10 mRNA level in allograft and prevented IP-10 secretion by peripheral blood mononuclear cells (PBMC) isolated from recipient rats seven days posttransplantation. Furthermore, in vitro experiments demonstrated that PrA addition to control PBMC prevented IP-10 secretion. Chemotactic migration assays were utilized to evaluate recipient T cell migration towards PBMC supernatant. PrA administration impaired PBMC supernatant-induced T cell migration. Additional in vitro experiments revealed that PrA slightly reduced naïve T cell migration towards chemokines. The presence of IP-10 in PBMC supernatant prevented PrA from reducing T cell migration in PrA-treated recipients. Neither CXCR3 chemokine ligand Mig nor non-CXCR3 chemokine ligand SDF-1 had any effect on T cell migration in PrA-treated recipients. The addition of anti-CXCR3 antibody restored PrA-mediated inhibition of T cell migration. Immunofluorescence microscopy showed that IP-10 was expressed mainly in CD68 positive infiltrating monocytes. Furthermore, PrA consistently reduced CXCR3+T cell infiltration into cardiac allografts. The reduced intensity of CXCR3 staining in PrA-treated allografts contributed to the previously depressed naïve T cell migrating activity induced by PrA. Collectively, these data indicate that PrA inhibition of IP-10 activity reduced recipient T cell migration and infiltration of cardiac allografts, thus partially explaining the immunosuppressive effect of PrA.
    PLoS ONE 05/2014; 9(5):e96138. DOI:10.1371/journal.pone.0096138 · 3.23 Impact Factor
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    • "Accumulation of ROS increases cellular/replicative senescence in these progenitors as does increased angiotensin II, oxidized low-density lipoprotein (ox-LDL) and homocysteine. EPCs of diabetic origin show a reduced ability to integrate into EC tubes in vitro compared to EPCs of non-diabetic origin [38–40]. Vascularization is depressed when EPCs from STZ treated mice are injected into normal mice [41]. "
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    ABSTRACT: The outcome of liver transplantation is steadily improving. Still there is need for earlier detection of complications like hepatic artery thrombosis and rejection. The aim of this study was to explore whether microdialysis with a 100-kDa cutoff filter could be used to monitor local inflammation after liver transplantation. Twenty patients undergoing liver transplantations were observed for 1 week posttransplant. Microdialysis catheters were introduced in each liver lobe subcutaneously and metabolic parameters (glucose, pyruvate, glycerol, and lactate), cytokines (interleukin [IL]-6, IL-8, monocyte chemottractic protein-1, and inducible protein [IP]-10), and complement activation (C5a) were measured. Fourteen patients experienced an uneventful course, judged clinically by ultrasound Doppler and by metabolic markers including lactate and the ischemia indicator lactate-to-pyruvate ratio. All patients with uneventful course had a consistent rise in IP-10 from 200 to 3000 pg/mL after transplantation, whereas the other cytokines stayed low. Two patients with rejection showed a selective increase in IL-8 and C5a, starting 2 to 4 days before alanine transferase increased, reaching 10- to 50-fold increase compared with baseline levels, and decreased rapidly after start of antirejection therapy. C5a concentration was substantially increased in these two patients at the time of transplantation. A third patient developed a hepatic artery thrombosis and rejection and showed a rapid rise in intrahepatic lactate and a complex inflammatory pattern. Microdialysis using a 100-kDa filter is a promising way of monitoring the inflammatory reaction after liver transplantation. Increase in IP-10 reflects a normal pathophysiologic response posttransplant, whereas IL-8 and C5a were increased only in patients with rejection.
    Transplantation 11/2008; 86(8):1096-103. DOI:10.1097/TP.0b013e31818775ca · 3.83 Impact Factor
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