THE ACTION OF SLPI ON TUBULAR EPITHELIAL CELLS AND IMMUNE RESPONSE PROTECS THE KIDNEY OF TRANSPLANT PATIENTES

AMBROSI, N; REMOLINS, C.; ROMEO, H.; UVA, P.; RÉ, L.; INCARDONA, C.; CASADEI, D.; CHULUYAN, E.; GUERRIERI, D.

Congreso; ANNUAL MEETING OF BIOSCIENCE SOCIETIES 2021; 2021

Secretory leukocyte protease inhibitor (SLPI) is a serine protease inhibitor with pleitropic activities on immune and non-immune cells. Lately, it has been proposed SLPI as a biomarker of acute kidneyinjury with a protective role on tubular epithelial cells. The aim of the present work was to unravel whether SLPI action on kidney is an immune mediated effect. We found that the administration of SLPI reduced the kidney damage in a rat model of ischemia reperfusion injury. However, SLPI was also able to reduce the damage in a gentamicin-induced nephrotoxicity rat model. In in vitro experiments, the HK-2 human epithelial cells-treatment with SLPI reduced the cell apoptosis induced by serum starving conditions or calcineurin inhibitors. A real-time PCR array data with HK-2 cells revealed that SLPI modulated transcript levels of genes mainly involved in DNA repair, response to misfolded proteins and inflammatory response pathways. Furthermore, SLPI favors the proliferation and migration of HK-2 cells. In kidney transplant patients, plasma levels of SLPI were high and indirectly associated with kidney function but also with leukocyte proliferation index. However, the levels of SLPI transcripts found in the renal biopsies were indirectly associated withplasma creatinine and TGFb but directly associated with HMOX-1.An indirect association was found between plasma levels of FK506 and SLPI. These results confirm that local SLPI exert a protective role in kidney transplant patients which can be mediated directlyon epithelial cells and indirectly by affecting the immune response. Furthermore, it suggests that immunosuppression treatment can reduce the expression of this nephropotective factor.