共查询到20条相似文献,搜索用时 31 毫秒
1.
Soule JL Streblow DN Andoh TF Kreklywich CN Orloff SL 《Transplantation proceedings》2006,38(10):3214-3220
BACKGROUND: Studies have shown that rat cytomegalovirus (RCMV) infection accelerates transplant vascular sclerosis (TVS) in rat heart and small bowel allotransplants. In these models, RCMV-accelerated TVS results from increased graft infiltration of inflammatory cells through up-regulation of chemokine expression. The aim of this study was to determine if RCMV infection accelerates renal transplant chronic allograft nephropathy (CAN), and the role of chemokines in this process. METHODS: F344 kidneys were transplanted into Lewis recipients with and without RCMV infection. To monitor CAN, serum creatinine (Cr) levels were measured starting at 4 weeks posttransplantation. At 7 and 21 days, and at terminal rejection, grafts were examined for histologic changes, inflammatory cell infiltrates, viral load, and chemokine expression profiles. RESULTS: By week 8, serum Cr showed significant elevation (P < .01) in the RCMV-infected group vs uninfected group, and remained significantly elevated through the end of the study. RCMV+ renal allografts had significant inflammatory cell infiltration and increased CAN at postoperative day (POD) 28. The CC chemokines RANTES, MCP-1, and MIP-1alpha, and the CXC chemokine IP-10 were up-regulated in RCMV-infected vs uninfected allografts. IP-10 was significantly up-regulated early in the process, whereas RANTES and MCP-1 were induced at a later time. CONCLUSIONS: RCMV infection accelerates CAN, with associated graft inflammatory infiltrates, which is paralleled by an increase in expression of CC and CXC chemokines. Our findings suggest that the early induction of IP-10 in the infected allografts promotes alterations in T-cell and monocyte migration to the graft, which initiates accelerated inflammatory and fibrotic changes associated with CAN. 相似文献
2.
Pribylova-Hribova P Kotsch K Lodererova A Viklicky O Vitko S Volk HD Lacha J 《Kidney international》2006,69(10):1872-1879
3.
4.
Kaminska D Tyran B Mazanowska O Letachowicz W Kochman A Rabczynski J Szyber P Patrzalek D Chudoba P Klinger M 《Transplantation proceedings》2005,37(2):767-769
The aim of our study was to correlate intragraft mRNA expression of cytokines and growth factors with histopathologic features in renal allograft biopsies. Fifty-six core biopsies performed in 51 kidney transplant recipients were assessed by the Banff '97 classification. Tubular and glomerular expressions of IFN-gamma, TGF-beta1, and PDGF-B as well as IL-2, IL-6, and IL-10 mRNA were assessed using semiquantitative RT-PCR in situ. No significant differences were noted between acute cellular and vascular rejection with regard to the glomerular and tubular mRNA expression of cytokines examined. We observed a positive correlation between tubular and glomerular IL-10 and IFN-gamma mRNAs during acute rejection. In chronic rejection the mRNA expression levels of IFN-gamma and IL-2, IL-6, and IL-10 did not differ from those of acute rejection; moreover, the glomerular expression of mRNA for TGF-beta1 (P < .05) and PDGF-B (P < .1) was even lower than during acute rejection episodes. Both tubular and glomerular IL-2, TGF-beta1, and PDGF-B mRNA expression levels in biopsies with acute rejection were significantly higher than in acute tubular necrosis (ATN). Biopsy samples with borderline changes exhibited the lowest levels of cytokine gene expression and were close to the intensity of control specimens obtained from living donor kidney biopsies taken during organ harvest. Our data failed to show a dichotomy between Th1 and Th2 cytokine activation in biopsy specimens from kidney allograft recipients; both Th1- and Th2-derived cytokines were involved to similar extents in rejection processes. 相似文献
5.
Nikolova PN Ivanova MI Mihailova SM Myhailova AP Baltadjieva DN Simeonov PL Paskalev EK Naumova EJ 《Transplant immunology》2008,18(4):344-348
Chronic allograft nephropathy (CAN) is one of the main causes of graft loss in renal transplantation. Polymorphisms with functional significance in the promoter and coding regions of cytokine genes have been suggested as a possible factor for graft rejection. The aim of this study was to investigate the impact of cytokine gene polymorphism of pro and anti-inflammatory cytokines on development of CAN in a group of renal transplant patients and donors. Eight single nucleotide polymorphisms (SNPs) including TNFA (-308), TGFB1 (cdns10, 25), IL-10 (-1082, -819, -592), IL-6 (-174) and IFNG (+874) were analyzed in 56 patients with stable graft function (SGF), 10 with CAN and 28 kidney donors by PCR-SSP method. CAN was significantly associated with the recipient TGFB1 cod10 T/T and combination of cods10, 25 T/T G/G genotypes (high producer), (p<0.05). Influence of patient's TNFA genotype correlated with high level of gene expression on the development of CAN was further demonstrated when the patients were stratified according to the HLA mismatches (HLA-DRB MMs). Additionally donor TNFA-308 G/A (high) and IL-6-174 CC (low) genotypes were increased in cases with CAN. No statistically significant differences in distribution of IL-10, IL-6 and IFNG genotypes between recipients with SGF and CAN were found. In conclusion our data suggest that the high producer genotype of profibrogenetic TGF-beta1, pro-inflammatory TNF-alpha and genetically determined low production of immunoregulatory IL-6 cytokine might be risk factors for CAN development. 相似文献
6.
Poly(ADP-ribose) polymerase expression in kidney transplantation: from alfa (alpha) to Omega (Omega) 总被引:1,自引:1,他引:0
O'Valle F Gómez-Morales M Del Moral RM Serón D Moreso F Osuna A Oliver FJ Del Moral RG 《Transplantation proceedings》2007,39(7):2099-2101
INTRODUCTION: Overactivation of the enzyme poly(ADP-ribose) polymerase (PARP-1) can be induced by ischemia-reperfusion and involved in the renal injury subsequent to kidney transplant. The poly(ADP-ribosy)lation mechanism alters free radical-induced DNA damage, which is repair by PARP-1 polymer. However, PARP-1 overexpression induces cellular necrosis. Our aim was to study the immunohistochemical PARP-1 expression in kidney transplant biopsies associated with various events. MATERIALS AND METHODS: We studied the nuclear expression of PARP-1 in kidney tubule cells by immunohistochemistry using the monoclonal antibody PAR01 in donor biopsies without acute tubular necrosis (ATN) (n = 60; controls), allografts that suffer ATN (n = 90) or an episode of acute humoral rejection (n = 12) or acute tubulointerstitial rejection (n = 25), or chronic allograft nephropathy (n = 25). Furthermore, we also studied protocol biopsies with subclinical rejection (n = 60). Renal lesions in transplant biopsies were graded blindly using 1997 Banff criteria without any clinical information. RESULTS: Biopsies without morphological features of ATN, namely acute tubulointerstitial rejection, borderline or subclinical rejection, showed lesser PARP-1 expression compared with biopsies with ATN or with ischemic mechanism of acute humoral rejection or chronic allograft nephropathys. We observed an inverse relation between PARP-1 expression and renal function (P < .001). Overall, renal biopsies showing ATN revealed greater expression of PARP-1 (r = 0.785, Pearson test). A significant relationship with PARP-1 expression was demonstrated with renal function (effective diuresis, serum creatinine levels) and pretransplant cold ischemia time (P < .001). CONCLUSION: Kidney transplant events including ischemia were associated with the highest PARP-1 expression and worse allograft renal function. 相似文献
7.
Lacha J Hribova P Kotsch K Brabcova I Bartosova K Volk HD Vitko S 《Transplantation proceedings》2005,37(2):764-766
Posttransplantation alloantigen-dependent and alloantigen-independent processes are both mediated by cytokines and chemokines. Recently cytokines and chemokines, as well as their receptors, have been shown to be highly polymorphic. The cytokine and chemokine gene polymorphisms are associated with variable production, activity, expression, or ligand-receptor affinity. The aim of our study was to analyze the relation between selected cytokine and chemokine gene polymorphisms in kidney donors and recipients as a function of donor-recipient match and posttransplantation outcome. Polymorphisms transforming growth factor-beta (TGF-beta); tumor necrosis factor-alpha (TNF-alpha); interleukin (IL)-6, and IL-10; monocyte chemoattractant protein-1 (MCP-1); and RANTES (regulated upon activation, normal T-cell expressed and secreted) genes were determined using DNA polymerase chain reaction technology in 268 healthy volunteers, 345 kidney transplant recipients (1997 to 1999), and 298 cadaveric donors. Patients were followed up for 4 to 6 years. The distribution of alleles of selected genes was identical in control subjects, cadaveric donors, and recipients. Low TGF-beta production in both the donor and recipient genotypes was associated with risk for early rejection (6 months) and worse graft function at 4 years. The only tendency for worse graft outcome was observed among donor-recipient combinations mismatched for TGF-beta genotype. Genetic determination of TNF-alpha and IL-10 production was associated with delayed graft function and rejection. IL-6 gene polymorphisms had no effect on the incidence of early acute rejections, but was associated with worse 5-year outcomes. Determinations of MCP-1 overproduction and RANTES-109 TT allele were associated with significant deterioration of graft function. Our data support the hypothesis that the strength of the alloimmune response after transplantation is in part genetically determined. Donor-recipient matching of cytokine gene polymorphisms has a marginal effect. 相似文献
8.
BACKGROUND: Allograft tolerance might be achieved by expressing immunomodulatory proteins through gene therapy. We have evaluated the possibility of promoting significantly allograft survival in a vascularized cardiac allograft model by performing ex vivo gene transfer. We used a lentiviral vector encoding the chemokine antagonist RANTES 9-68 that is capable of competing with native RANTES. METHODS: The Fisher donor/Lewis recipient rat strain combinations were used and all animals received for the first 5 days posttransplantation a subtherapeutic dose of cyclosporine A (1.5 mg/kg). Ex vivo gene transfer into heart allograft was performed by multiple injections of the SIN.cPPT lentiviral vector, which corresponds to the multiply attenuated, self-inactivating lentivector derived from the human immunodeficiency virus (HIV)-1. RESULTS: About 6% of the cardiac tissue had integrated lentiviral vector, which closely matches the mean in vivo RANTES antagonist expression of 5% obtained by immunohistochemistry. In vivo RANTES 9-68 expression has significantly prolonged graft survival (median [25%-75%]: 20 [17-26] days), compared to the control 15 ([14-15] days; P=0.0007). Furthermore, hearts transduced with RANTES 9-68 showed a significant (P<0.05) reduction in cell infiltration and intragraft expression of TNF-alpha, IFN-gamma, endogenous RANTES, and TGF-beta. CONCLUSION: Lentiviral gene transfer of RANTES 9-68 antagonist attenuates significantly the inflammatory response and delays allograft rejection, despite low levels of transduction. Future improvement of heart transduction by lentiviral vectors, as it has been achieved with other vectors, might become an attractive alternative therapy for treating allografts that require sustained gene expression for better organ preservation. 相似文献
9.
Cytokine and chemokine expression kinetics after corneal transplantation 总被引:17,自引:0,他引:17
10.
Baker MS Chen X Rotramel AR Nelson JJ Lu B Gerard C Kanwar Y Kaufman DB 《Surgery》2003,134(2):126-133
BACKGROUND: Interaction of chemokine receptor CXCR3 with its ligand IP-10 mediates effector cell trafficking to sites of allograft rejection in murine models of whole organ allotransplantation. We hypothesized that blocking the CXCR3/IP-10 interaction would impair posttransplantation leukocyte trafficking to and delay rejection of pancreatic islet allografts. METHODS: A/J strain murine islets were implanted to the kidney capsule of H-2 disparate, streptozotocin-induced diabetic wild type (WT), CXCR3 deficient (CXCR3(-/-)) or IP-10 antibody-treated WT (alphaIP-10) C57BL/6 recipients. Representative grafts from each group were harvested at day 7. Ribonuclease protection assay was used to determine gene expression for cell markers F4/80 (macrophages), CD8 (type I T cells), CD4 (type II T cells), and CD 19 (natural killer cells), and for chemokines IP-10, MIP-1alpha, MIP-1beta, MCP-1, and RANTES. Immunohistochemistry was used to confirm ribonuclease protection assay infiltrate data. Graft-site chemokine gene expression and cellular infiltrate were correlated with time to functional graft rejection. RESULTS: Untreated WT recipients demonstrated heavy graft-site cell infiltrates and increased graft-site gene expression for cell markers F4/80, CD8, CD4, and CD19, and for chemokines RANTES, IP-10, and MIP-1beta at day 7. In comparison with untreated WT, alphaIP-10-treated WT and CXCR3(-/-) recipients demonstrated the same degree of chemokine gene expression but less lymphocytic infiltrate. The mean length of allograft survival was 12.7 +/- 3.1 days in untreated WT versus 20.2 +/- 2.7 days (P <.05) for CXCR3(-/-)- and 19.7 +/- 2.3 days (P <.05) for alphaIP-10-treated WT recipients. CONCLUSIONS: CXCR3 gene deletion or alphaIP-10 antibody therapy modulates posttransplantation lymphocytic graft infiltration and statistically prolongs graft survival in murine islet allograft recipients. 相似文献
11.
BACKGROUND: To assess short- and long-term influence of the TGF-beta1 on renal allografts. METHODS: Expression of TGF-beta1 and TNF-alpha, and the proportion of macrophages and eosinophils in interstitium were evaluated in 64 cases including five cases with nonrejected kidneys (NRK), 18 cases with acute rejection (AR), 26 cases with chronic allograft nephropathy (CAN), and 15 cases with acute cyclosporine A (CsA) toxicity. Follow-up biopsies of all cases with AR and CsA toxicity were evaluated for development of interstitial fibrosis (IF) and graft atherosclerosis (GAS). Additionally, influence of tubular-TGF-beta1 expression on graft function during 6 months after the diagnostic biopsy was evaluated. RESULTS: A significant differences was seen between rejected kidneys and acute CsA toxicity in regards of tubular TGF-beta1 expression that patients with CsA toxicity exhibited significantly higher grade of tubular TGF-beta1 expression than patients with AR (P<0.05) and CAN (P<0.05). A significant difference was found between the grades of tubular TGF-beta1 expression in regards to graft function of cases with AR and CsA toxicity (P<0.05). Higher grade tubular TGF-beta1 expression showed better graft function during 6 months. Besides the degree of renal TGF-beta1 expression was positively correlated with development of diffuse IF and GAS (P<0.05) that the risk of the IF and GAS was higher in cases with grade 2 renal TGF-beta1 expression. CONCLUSIONS: Despite the short-term posttransplantation tubule-repairing effects of TGF-beta1, the overall effects of TGF-beta1 in the kidney seem to be negative that increased expression of TGF-beta1 promotes IF and vasculopathy associated with CAN. 相似文献
12.
Kim JY Kim D Lee EM Choi I Park CG Kim KS Ha J Kim SJ Yang J Kim YS Han JS Kim S Lee JS Ahn C 《Transplant immunology》2003,12(1):63-72
To elucidate the possible immunoregulatory role of nitric oxide (NO) in cellular xenograft rejection we performed rat-to-mouse skin xenotransplantation. The rat skin engrafted mice were treated with the inducible NO synthase (iNOS) inhibitors, aminoguanidine (AMG, 200 mg/kg) and NG-nitro-L-arginine methyl ester (L-NAME, 60 mg/kg) every other day until rejection. Skin xenograft survival was monitored and immune cell infiltration and intragraft cytokine and chemokine mRNA expressions were analyzed 7 days after grafting. Compared with the control mice, the AMG- and L-NAME treated mice showed delayed xenograft rejection by approximately 3 days (8.9 +/- 0.7 days vs. 11.7 +/- 1.2 and 12.0 +/- 0.9 days, respectively). Infiltrations of CD11b+, MOMA-2+ cells and neutrophils were significantly reduced in both AMG- and L-NAME treated graft but CD4+ and CD8+ cells were not. The expression of cytokines such as IL-1beta, IL-2, IL-6, IL-12 and IFN-gamma in AMG- and L-NAME treated grafts were significantly decreased (P<0.01), whereas IL-10, TNF-alpha and TGF-beta1 were unchanged or enhanced. Additionally, the expressions of CC-chemokines, such as RANTES and MIP-1alpha, were significantly reduced (P<0.01) whereas the expressions of CXC-chemokines, such as IP-10 and MIG, were unchanged. These results imply that prolonged rat-to-mouse skin xenograft survival by iNOS inhibitors may be due to the selective inhibition of pro-inflammatory cytokines and chemokines and suggest the possible regulatory role of NO in cytokine and chemokine expressions during xenotransplant rejection. 相似文献
13.
BACKGROUND: The beta-chemokines MCP-1 (CCL2) and RANTES (CCL5) have been shown to play important roles in acute renal transplant rejection (AR) and chronic allograft nephropathy (CAN). The potential relationship of expression of these chemokines, their chemokine receptors CCR1, CCR2, CCR5, and the cell populations of inflammatory infiltrate, histological and clinical diagnoses were investigated in biopsies at the time of AR and compared with biopsies of CAN. METHODS: In 24 renal transplant biopsies with AR (n = 15) and CAN (n = 9), the expression of MCP-1 and RANTES, their receptors CCR1, CCR2, and CCR5 and the infiltration with monocytes/macrophages and T cells were studied. RESULTS: As previously described, chemokine and chemokine receptor expression was found mainly in mononuclear cells infiltrating the interstitium and glomeruli. In the tubulointerstitial area and glomeruli the expression of MCP-1, RANTES, and their receptors correlated with an infiltration by monocytes/macrophages. Biopsies with CAN revealed a lower expression of MCP-1, RANTES, CCR1, CCR2 and CCR5 in tubulointerstitial cells, and a significantly lower infiltration with MRP14-positive monocytes/macrophages than biopsies with AR. In AR, MCP-1 and CCR1 showed a lower expression compared to RANTES, CCR2, and CCR5. CONCLUSIONS: The positive correlation between chemokines and chemokine receptors and infiltrating leukocytes during acute rejection, the lower but detectable expression of MCP-1, RANTES, CCR1, CCR2 and CCR5 in CAN, and the differences in the quantity of expression between the different chemokines and chemokine receptors point to a complex regulation of chemokine expression in renal allografts. Since chemokines are not only involved in inflammation but also in tissue regeneration, this could have impact on the development of CAN. 相似文献
14.
Detection of cardiac allograft rejection by real-time PCR analysis of circulating mononuclear cells 总被引:4,自引:0,他引:4
BACKGROUND: Detection of cardiac allograft rejection is based on the histological examination of endomyocardial biopsies (EMB). We have explored the possibility of whether graft rejection could be detected by characteristic gene expression patterns in peripheral blood mononuclear cells (PBMC) of heart-transplant recipients. METHODS: The study included 58 blood samples of 44 patients. On the day of EMB, mononuclear cells were isolated from peripheral blood, and gene expression was measured by quantitative real-time PCR. Thirty-nine parameters, including cytokine and chemokine genes were analyzed. Gene expression results were correlated with histological assessment of concomitant evaluated EMB according to International Society for Heart and Lung Transplantation (ISHLT) nomenclature. RESULTS: Gene expression of perforin, CD95 ligand, granzyme B, RANTES, CXCR3, COX2, ENA 78 and TGF-beta1 was significantly different in PBMC of patients with mild to moderate degrees of allograft rejection (> or =grade 2) compared with patients exhibiting no or minor forms of rejection ( or =grade 2 vs. 相似文献
15.
Karasu Z Ulukaya S Ayanoglu HO Basturk B Ulukaya E Akyildiz M Tokat Y 《Transplantation proceedings》2004,36(9):2791-2795
Cytokines, which play important roles in allograft rejection, show variable production among individuals. These variations may be related to genetic polymorphisms within the regulatory regions of the cytokine genes. We investigated the association between the role tumor necrosis factor alpha (TNF-alpha), transforming growth factor-beta (TGF-beta), interferon gamma (IFN-gamma), interleukin (IL)-10 and IL-6 gene polymorphisms and early graft rejection among liver transplant recipients. Forty-three liver transplant recipients enrolled in this study were divided into 2 groups based on events in the first 2 months posttransplantations, namely, those experiencing at least 1 rejection episode (n = 26) or those without any episode (n = 17). The allele or genotype frequencies of cytokine gene polymorphisms showed no difference between liver recipients with or without nonrejection. In conclusion, there was no significant correlation between early graft rejection and cytokine gene polymorphism of TNF-alpha, TGF-beta, IL-10, IL-6, and IFN-gamma in liver transplant recipients. 相似文献
16.
Song E Zou H Yao Y Proudfoot A Antus B Liu S Jens L Heemann U 《Kidney international》2002,61(2):676-685
BACKGROUND: Initial insults to kidney allografts, characterized by infiltration of mononuclear inflammatory cells, contribute to chronic allograft nephropathy. Chemokines such as RANTES (regulated upon activation, normal T cell expressed) are thought to be responsible for the recruitment and activation of infiltrating cells. The present study investigated whether early application of Met-RANTES, a chemokine receptor antagonist that blocks the effects of RANTES, can protect renal allografts from long-term deterioration. METHODS: Fisher (F344) rat kidneys were orthotopically transplanted into Lewis recipients and treated with cyclosporine A (1.5 mg/kg/day) for the first 10 days following transplantation, together with either Met-RANTES at 40 microg/day, 200 microg/day or vehicle for the first 7 days. Animals were harvested at 2 and 28 weeks after transplantation for histologic, immunohistologic and molecular analysis. RESULTS: Met-RANTES treatment reduced the infiltration of lymphocytes and macrophages in allografts at 2 weeks after transplantation, accompanied by decreased mRNA expression of interleukin (IL)-2, IL-1beta, tumor necrosis factor-alpha (TNF-alpha) and RANTES. At post-transplantation week 28, Met-RANTES treatment at high and low doses reduced urinary protein excretion and significantly ameliorated glomerulosclerosis, interstitial fibrosis, tubular atrophy, intimal proliferation of graft arteries and mononuclear cell infiltration. However, creatinine clearance was not influenced by Met-RANTES. Furthermore, Met-RANTES suppressed the mRNA expression of transforming growth factor-beta (TGF-beta) and platelet-derived growth factor-B (PDGF-B). CONCLUSIONS: Blockade of chemokine receptors by Met-RANTES diminishes early infiltration and activation of mononuclear cells in the grafts, and thus reduces the pace of chronic allograft nephropathy. 相似文献
17.
Lee S Kim DJ Park MG Park SK Kim JS Hyun SJ Oh JE Nam ES Joo SH 《Transplantation proceedings》2008,40(7):2147-2148
Chronic allograft nephropathy (CAN) includes pathologic changes of interstitial fibrosis, tubular atrophy, and fibrous intimal thickening. Transforming growth factor (TGF)-beta1 is a fibrogenic cytokine involved in renal allograft fibrosis. Hypoxia-inducible factor (HIF)-1alpha is induced as an adaptive response to hypoxia triggering the production of fibrogenic cytokines such as TGF-beta1. Between January 1995 and February 2005, we performed 71 renal allograft biopsies in 61 recipients. Immunohistochemical studies were performed with an immunoperoxidase technique using as the primary antibody either a rabbit anti-human TGF-beta1 polyclonal or a mouse anti-human HIF-1alpha monoclonal reagent. The glomerular TGF-beta1 expression in recipients diagnosed with glomerulonephritis was significantly greater than other pathologic groups (P < .05), and the glomerular TGF-beta1 expression in the heavy proteinuria group (>/=2.5 g/d) was significantly greater than the low proteinuria group (<1.0 g/d; P < .05). The tubular and interstitial TGF-beta1 and HIF-1alpha expressions in CAN were greater than in other groups (P < .05). The tubular TGF-beta1 expression among the graft loss group was significantly greater than the graft function group (P < .05). 相似文献
18.
Pawlik A Domanski L Rozanski J Florczak M Wrzesniewska J Dutkiewicz G Dabrowska-Zamojcin E Gawronska-Szklarz B 《Transplant immunology》2005,14(1):49-52
Chronic allograft rejection remains an important cause of morbidity after kidney transplantation. The aim of the study was to examine the association between IL-2, IL-6 and TNF-alpha promoter polymorphisms and chronic kidney allograft rejection. The study included 64 patients with long-term stable graft function and 62 with chronic allograft nephropathy. Among patients with chronic allograft nephropathy a statistically significant prevalence of the IL-6 CC genotype associated with low IL-6 expression was observed (p < 0.01, OR 3.18; 95% CI 1.27-8.15). There were no statistically significant differences in distribution of IL-2 and TNF-alpha genotypes between patients with stable graft function and chronic allograft rejection. The results of present study suggest that the genetically determined low IL-6 production may be the risk factor of chronic allograft nephropathy development. 相似文献
19.
BACKGROUND: Delayed graft function is primarily caused by acute tubular necrosis (ATN). We studied in renal transplant recipients with posttransplant graft biopsy whether an up-regulated immune system in the recipient immediately before transplantation affects the risk of developing ATN and might be relevant for the pathogenesis of ATN. METHODS: In a retrospective study, we analyzed pretransplant and early posttransplant soluble interleukin (sIL)-1RA, interleukin (IL)-2, sIL-2R, IL-3, IL-4, IL-6, sIL-6R, IL-10, tumor necrosis factor (TNF)-alpha, transforming growth factor (TGF)-beta2, interferon (IFN)-gamma, and neopterin plasma levels in patients with ATN (n=26). Matched patients with acute rejection (AR) (n=26) or normal posttransplant biopsy (n=26) served as controls. RESULTS: Pretransplant sIL-6R was higher (P=0.0004) and pretransplant TGF-beta2 lower (P=0.002) in patients with ATN than in patients with normal biopsy. ROC curves showed that high pretransplant sIL-6R has a high sensitivity (77%) and high specificity (64%) for ATN (P=0.002). Posttransplant plasma sIL-6R continued to be higher in ATN patients than in patients with normal biopsy (P=0.001). Patients with acute rejection showed pre- and posttransplant sIL-6R and TGF-beta2 plasma levels similar to those of patients with normal biopsy (P=NS). CONCLUSION: High pretransplant sIL-6R plasma levels are associated with an increased risk of ATN and might contribute to the development of ATN early posttransplant. Our data suggest that preactivation of the recipient's immune system increases the risk of ATN. 相似文献
20.
Proinflammatory cytokines induce NF-kappaB-dependent/NO-independent chemokine gene expression in MIN6 beta cells 总被引:2,自引:0,他引:2
Baker MS Chen X Rotramel A Nelson J Kaufman DB 《The Journal of surgical research》2003,110(1):295-303
BACKGROUND: Interactions between chemokines IP-10, MCP-1, and RANTES and their receptors may mediate graft rejection following islet transplantation. The mechanisms regulating chemokine gene expression in pancreatic islet cells have not been well characterized. We examined the cytokine-induced gene expression profiles for several chemokines in a transformed pancreatic beta-cell line (MIN6) cotreated with an inhibitor of nitric oxide synthase and in a mutated clone of MIN6 made to overexpress a dominant negative inhibitor of NF-kappaB (IkappaBalphaM). METHODS: MIN6 and MIN6-IkappaBalphaM (Bm) cells were cultured in mixtures of IL-1beta and TNF-alpha or IL-1beta, TNF-alpha, and IFN-gamma plus/minus the iNOS inhibitor L-NMMA. RT-PCR and RNase Protection Assay were used to measure mRNA expression for the following chemokines: IP-10, MIP-1alpha, MIP-1beta, MCP-1, and RANTES. Enzyme linked immunosorbant assay was used to measure IP-10 and MCP-1 protein release. RESULTS: Cytokine-treated MIN6 and Bm demonstrated increased expression of genes for IP-10 and MCP-1. Expression in MIN6 was first detected at 2 h of incubation and peaked at 6 h. MIN6 demonstrated a more marked increase in chemokine gene expression for both IP-10 and MCP-1 and a more marked increase in IP-10 protein release than did Bm. There was no detectable gene expression for MIP-1alpha, MIP-1beta, or RANTES from MIN6 or Bm. L-NMMA completely blocked NO production from MIN6 and Bm but had no effect on chemokine gene expression in either MIN6 or Bm. CONCLUSIONS: These results suggest that beta cells produce a complement of rejection-relevant chemokines in response to a proinflammatory stimulus and that pathways governing cytokine-induced chemokine gene expression in MIN6 are dependent on NF-kappaB but independent of NO. 相似文献