SLPI Induces FOXP3- Regulatory T Cells and Decreases Acute Kidney Injury

GUERRIERI DIEGO; ROMEO HORACIO; AMBROSI NELLA; LANCARFONI MARCELA; RUFOLO CECILIA; ZANELLI GUSTAVO; INCARDONA CLAUDIO; CHULUYAN EDUARDO; CASADEI DOMINGO

San Francisco

Congreso; World Transplant Congress 2014; 2014

ASTS, TTS, AST

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.