TITLE

Activation of counter-regulatory mechanisms in a rat renal acute rejection model

AUTHOR(S)
Edemir, Bayram; Kurian, Sunil M.; Eisenacher, Martin; Lang, Detlef; Müller-Tidow, Carsten; Gabriëls, Gert; Salomon, Daniel R.; Schlatter, Eberhard
PUB. DATE
January 2008
SOURCE
BMC Genomics;2008, Vol. 9, Special section p1
SOURCE TYPE
Academic Journal
DOC. TYPE
Article
ABSTRACT
Background: Microarray analysis provides a powerful approach to identify gene expression alterations following transplantation. In patients the heterogeneity of graft specimens, comorbidity, co-medications and the challenges in sample collection and preparation complicate conclusions regarding the underlying mechanisms of graft injury, rejection and immune regulation. Results: We used a rat kidney transplantation model with strict transplant and sample preparation procedures to analyze genome wide changes in gene expression four days after syngeneic and allogeneic transplantation. Both interventions were associated with substantial changes in gene expression. After allogeneic transplantation, genes and pathways related to transport and metabolism were predominantly down-regulated consistent with rejection-mediated graft injury and dysfunction. Up-regulated genes were primarily related to the acute immune response including antigen presentation, T-cell receptor signaling, apoptosis, interferon signaling and complement cascades. We observed a cytokine and chemokine expression profile consistent with activation of a Th1-cell response. A novel finding was up-regulation of several regulatory and protective genes after allogeneic transplantation, specifically IL10, Bcl2a1, C4bpa, Ctla4, HO-1 and the SOCS family. Conclusion: Our data indicate that in parallel with the predicted activation of immune response and tissue injury pathways, there is simultaneous activation of pathways for counter regulatory and protective mechanisms that would balance and limit the ongoing inflammatory/immune responses. The pathophysiological mechanisms behind and the clinical consequences of alterations in expression of these gene classes in acute rejection, injury and dysfunction vs. protection and immunoregulation, prompt further analyses and open new aspects for therapeutic approaches.
ACCESSION #
38123081

 

Related Articles

  • Toward novel antirejection strategies: In vivo immunosuppressive properties of CTLA4Ig. Perico, Norberto; Imberti, Ornella; Bontempelli, Mario; Remuzzi, Giuseppe // Kidney International;Jan1995, Vol. 47 Issue 1, p241 

    Allograft rejection is a process that depends on T cell receptor-ligand interaction and costimulatory signals generated when accessory molecules binds to their ligands, such as CD28 to the B7 molecules. We investigated the possibility that B7 blockade in vivo by the soluble CD28 receptor homolog...

  • Anti-Rejection Drugs may be Rejected by Some.  // Molecular Diagnosis & Therapy;Sep2007, Vol. 11 Issue 5, p339 

    The article reports on the results of a U.S.-based study which suggest that a specific genetic signature can possibly determine if organ transplant recipients could reduce or eliminate their lifelong dependence on immunosuppression therapy. The researchers examined gene expression patterns from...

  • HLA-A incompatibility associated with enhanced long- term renal graft survival in HLA-B, DR mismatched transplants. Bućin, D.; Ekberg, H.; Lindholm, A.; Persson, H.; Tufveson, G.; Albrechtsen, D. // Immunology & Cell Biology;Dec1994, Vol. 72 Issue 6, p455 

    The effect of HLA-A matching on long-term cadaver kidney graft survival was analysed, on average, 6 years after transplantation in a total of 1085 cyclosporine (CyA)-treated patients. A beneficial effect of HLA-A mismatching on graft survival was found by univariate and multivariate analyses (P...

  • Role of humoral presensitization in human renal transplant rejection. Gailiunas Jr., Peter; Suthanthiran, Manikkam; Busch, George J.; Carpenter, Charles B.; Garovoy, Marvin R. // Kidney International;May1980, Vol. 17 Issue 5, p638 

    A prospective study of 31 cadaveric renal allograft recipients was performed to determine the significance of pretransplant presensitization undetected by the conventional microlymphocytotoxicity crossmatch. Donor-specific humoral presensitization revealed by the antibody-dependent cell-mediated...

  • Screening panel-reactive antibody negative, single-antigen positive: a case report. Jawdat, Dunia; Al Qurashi, Salem; Al Sayyari, Abdulla; Hajeer, Ali H. // Progress in Transplantation;Dec2014, Vol. 24 Issue 4, p341 

    Sensitized patients remain a challenge for successful transplant. Virtual crossmatch is used to determine the presence or absence of donor-specific antibodies. A 60-year-old woman with a negative screening for panel-reactive antibodies (PRA) received an A*11, A*68 type kidney with a negative...

  • Screening strategies and predictive diagnostic tools for the development of new-onset diabetes mellitus after transplantation: an overview. Pham, Phuong-Thu T.; Edling, Kari L.; Chakkera, Harini A.; Pham, Phuong-Chi T.; Pham, Phuong-Mai T. // Diabetes, Metabolic Syndrome & Obesity: Targets & Therapy;2012 Part 2, Vol. 5, p379 

    New-onset diabetes mellitus after transplantation (NODAT) is a serious and common complication following solid organ transplantation. NODAT has been reported in 2% to 53% of all solid organ transplants. Kidney transplant recipients who develop NODAT have variably been reported to be at increased...

  • OUTCOME OF KIDNEY TRANSPLANTATION IN SECONDARY RENAL AMYLOIDOSIS: A SINGLE CENTRE EXPERIENCE. M. S., Rokade; U. N., Hegde; K., Gohel; S., Gang; M. M., Rajapurkar // Indian Journal of Nephrology;Jul-Sep2007, Vol. 17 Issue 3, p143 

    Background: Renal transplantation is regarded as the effective renal replacement therapy in patients with renal amyloidosis. Aim: This retrospective study was done to investigate the results of kidney transplantation in patients with secondary renal amyloidosis. Materials and Methods: We studied...

  • Agonistic Autoantibodies and Rejection of Renal Allografts. Ingelfinger, Julie R. // New England Journal of Medicine;2/10/2005, Vol. 352 Issue 6, p617 

    Presents an editorial on the rejection of allografts in renal transplantation. Belief that certain antibodies against HLA antigens have been considered to be the factor that initiates acute rejection; Description of a study in this issue by Dragun and others that reports on the presence of...

  • Low serial serum neopterin does not predict low risk for chronic renal graft rejection. Müller, Thomas; Orgler, Alexandra; Bidmon, Bettina; Arbeiter, Klaus; Balzar, Egon; Ruffingshofer, Dagmar; Aufricht, C. // Pediatric Nephrology;2001, Vol. 16 Issue 1, p11 

    Research has provided new and potent immunosuppressants which can potentially stop ongoing rejection. Subclinical rejection is a particular problem in the pediatric age group and early identification of children at risk is of the utmost importance. Neopterin has been previously shown to be a...

Share

Read the Article

Courtesy of THE LIBRARY OF VIRGINIA

Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics