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

DIEGO GUERRIERI, HORACIO ROMEO, NELLA AMBROSI, MARCELA LANFRANCONI, CECILIA RUFOLO, GUSTAVO ZANELLI, CLAUDIO INCARDONA, EDUARDO CHULUYAN, DOMINGO CASADEI.

Congreso; World Transplant Congress; 2014

Since ischemia reperfusion injury (IRI) remains a major problem in transplantation. Previous studies show that Secretory leukocyte protease inhibitor (SLPI) has immunomodulatory activity and its administration is protective in a model of autoimmune disease. The aim of the present study is to determine whether SLPI is protective in an animal model of renal ischemia reperusion injury and its possible mechanism of action. Materials and methods: renal ischemia/reperfusion was performed for 40 min in male SD rats, after 24 hours of reperfusion the animals were sacrificed and analyzed. Four experimental groups were performed: Control (with IRI and buffer); SLPI (IRI and SLPI) and SLPIi Group (IRI + SLPI no inhibitory activity) and Sham (animals without IRI). Treatment with SLPI or SLPIi was based on three doses of 250 g/kg ip (Scheme SLPI: 24 hours pre ischemia, at the time of ischemia and 6 h post- ischemia; Scheme SLPIpre: 48, 24 and 18 hours pre ischemia). Also a treatment was performed with in vitro culture of peripheral blood mononuclear cells (PBMC) treated with SLPI. Results: Both treatments with exogenous SLPI as PBMC treated animals pretreated with SLPI significantly reduced serum creatinine compared to control (control: 2.6 ± 1.0; SLPI: 1.2 ± 0.8; SLPIi: 0. 45 ± 0.41; pre SLPI: 0.45 ± 0.17; PBMC SLPI: 0.46 ± 0.1 mg / dl). A similar result was obtained when analyzing serum urea (Control: 143 ± 9; SLPI: 63 ± 27; SLPIi: 46 ± 23; SLPI pre: 43 ± 15; PBMC SLPI: 73 ± 18 mg / dl). The groups treated with SLPI or SLPIi showed a reduction in acute tubular necrosis and a significant decrease in the expression of TNF?, ED-1, MCP-1, CD86, CD14 and IL-10 (p < 0.05). Furthermore, pretreatment of human lymphocytes with SLPI generates cells with lymphocyte proliferation suppressor capacity without increasing levels of Foxp3 expression. Conclusion: This study demonstrates that treatment with SLPI improves clinical parameters, reduces necrosis in kidneys that have suffered ischemia and decreases the expression of proinflammatory genes by a mechanism independent of the serine protease activity and the generation of regulatory T cells.