BIOMED 24552
INSTITUTO DE INVESTIGACIONES BIOMEDICAS
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
SLPI Induces FOXP3- Regulatory T Cells and Decreases Acute Kidney Injury.
Autor/es:
D. GUERRIERI, H. ROMEO, N. AMBROSI, M. LANCARFONI, C. RUFOLO, G. ZANELLI, C. INCARDONA,E. CHULUYAN, D. CASADEI.; D. GUERRIERI, H. ROMEO, N. AMBROSI, M. LANCARFONI, C. RUFOLO, G. ZANELLI, C. INCARDONA, E. CHULUYAN, D. CASADEI.
Lugar:
San Francisco
Reunión:
Congreso; 2014 World Transplant Congress; 2014
Institución organizadora:
American Society of Transplantation and the American Society of Transplant Surgeons
Resumen:
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The ischemia reperfusion injury (IRI)
remains a major problem in renal transplantation. Previous studies show that
secretory leukocyte protease inhibitor (SLPI) has immunomodulatory activity and
protects from the injury caused by an autoimmune disease in rats. The aim of
the present study was to determine whether SLPI reduces the injury in an animal
model of renal ischemia reperfusion injury and its possible mechanism of
action. Renal ischemia/reperfusion was performed for 40 min in male rats. After
24 hours of reperfusion, the animals were sacrifi ced and analyzed. Four
experimental groups were performed: i) Control: with IRI; ii) SLPI: with IRI
and SLPI; iii) SLPIi: with IRI and SLPI without antiprotease activity; and iv)
Sham: rats without IRI. Treatments with SLPI or SLPIi were based on three doses
of 250 mg/kg ip and, two administration schemes: i) S1: 24 hours pre-ischemia,
at the time of ischemia and 6 h post- ischemia; and ii) S2: 48, 24 and 18 hours
pre ischemia. To unravel the mechanism, in another set of experiments, culture
cells (PBMC) were treated with SLPI in vitro, and then cells were administered
to the rats. Results: Both treatments (with SLPI and SLPI-treated cells)
signifi cantly reduced serum creatinine compared to control group (control: 2.6
± 1.0; SLPI (S1): 1.2 ± 0.8; SLPIi: 0.45 ± 0.41; SLPI (S2): 0.45 ± 0.17;
SLPI-treated cells: 0.46 ± 0.1 mg/dl). A similar result was obtained when
analyzing serum urea (Control: 143 ± 9; SLPI(S1): 63 ± 27; SLPIi: 46 ± 23;
SLPI(S2): 43 ± 15; SLPI-treated cells: 73 ± 18 mg/dl).The groups treated with
SLPI or SLPIi showed a reduction in acute tubular necrosisand a signifi cant
decrease in the expression of TNF?α, ED-1, MCP-1, CD86, CD14and IL-10 (p
<0.05). Furthermore, SLPI-pretreated cells induced Foxp3 negativecells,
which had the ability to reduce the lymphocyte proliferation. Conclusion:This
study demonstrates that SLPI reduces kidney IRI, which is independent of its
anti-protease activity; and suggests that the mechanism may be mediated by the
generation of unconventional regulatory T cells.
