Inhibition of mTOR Modulates SLPI Expression: A Potential Role in Kidney Transplant Patients
1CEFYBO, UBA, Buenos Aires, Argentina
2Fundacion 3er Milenio, INBA, Buenos Aires, Argentina
3UNICEN, Olavarria, Argentina
4Fundación GADOR, Buenos Aires, Argentina.
Meeting: 2015 American Transplant Congress
Abstract number: B287
Keywords: Graft function, Inflammation, Kidney transplantation, Rapamycin
Session Information
Session Name: Poster Session B: Vascularized Composite Tissue Allografts and Xenotransplantation
Session Type: Poster Session
Date: Sunday, May 3, 2015
Session Time: 5:30pm-6:30pm
Presentation Time: 5:30pm-6:30pm
Location: Exhibit Hall E
Secretory leukocyte protease inhibitor (SLPI) is a serine protease inhibitor secreted by inflammatory and epithelial cells. It functions as an endogenous immunomodulatory, with antiinflammatory and antimicrobial activity, and enhances wound healing.
The aim of the present work was to study the effect of mTOR inhibition on the expression of SLPI in vitro and in kidney transplanted patients treated with rapamycin.
Peripheral blood mononuclear cells (PBMC) derived from healthy donors (HD) were in vitro treated with PHA or a lysate of M. tuberculosis (Mtb) in the presence of rapamycin. After 24 h of culture, cell supernatants were harvested, and SLPI and cytokines were measured by ELISA and bead array assay. The plasma levels of SLPI and cytokines were measured in kidney transplanted patients, during the first year of the transplant treated with antithymocyte globulin, and an immunosuppressive maintenance therapy consisted of prednisone + MMF + rapamycin or prednisone + MMF + calcineurin inhibitor (CIN).
The inhibition of mTOR significantly increased the production of SLPI if the cells were previously treated with PHA or Mtb (p<0.01). This result suggest that SLPI is modulated by mTOR signaling. In order to determine the clinical implication of these findings, we next examine the levels of SLPI in kidney transplant patients treated with mTOR inhibitor or CIN. We observed that in the pre-transplant, the plasma levels of SLPI were higher than those found in HD subjects. Immediately after the transplant surgery, the SLPI levels decreased for CIN-treated patients but continued to be high for rapamycin-treated patients. However, the SLPI kinetics study showed that SLPI levels decreased in rapamycin-treated patients after 5 month of the surgery, reaching comparable values than those of CNI-treated patients.
Next we examined a possible associations between plasma SLPI values and kidney function parameters. Remarkably, we found a direct correlations between SLPI and creatinine and urea (p<0.01, r = 0.46).
Overall these results showed that mTOR signalling modulate the expression of SLPI. Furthermore, it is possible to speculate that, although SLPI induces a state of immune tolerance might also affect kidney function.
To cite this abstract in AMA style:
Ambrosi N, Dotta A, Pizarro C, Guerrieri D, Gonzalez A, Leiva C, Leon L, Mendiberri J, Rial M, Incardona C, Chuluyan E, Casadei D. Inhibition of mTOR Modulates SLPI Expression: A Potential Role in Kidney Transplant Patients [abstract]. Am J Transplant. 2015; 15 (suppl 3). https://atcmeetingabstracts.com/abstract/inhibition-of-mtor-modulates-slpi-expression-a-potential-role-in-kidney-transplant-patients/. Accessed November 21, 2024.« Back to 2015 American Transplant Congress