APOPTOSIS AND CHEMOKINE INDUCTION AFTER RENAL ISCHEMIA-REPERFUSION1
MARC Daemen, B de Vries, C van't Veer… - …, 2001 - journals.lww.com
MARC Daemen, B de Vries, C van't Veer, TGAM Wolfs, WA Buurman
Transplantation, 2001•journals.lww.comBackground. One of the earliest prerequisites for the development of inflammation after
ischemia-reperfusion (I/R) is local chemokine expression. We recently demonstrated that
apoptosis, characterized by intracellular caspase-activation, contributes to the development
of inflammation after I/R. Methods. The contribution of apoptosis was investigated using the
pan-caspase inhibitor Z-Val-Ala-Asp (OMe)-CH 2 F in a murine model of renal I/R. Renal
expression of the chemokines macrophage inflammatory protein-2 (MIP-2) and KC was …
ischemia-reperfusion (I/R) is local chemokine expression. We recently demonstrated that
apoptosis, characterized by intracellular caspase-activation, contributes to the development
of inflammation after I/R. Methods. The contribution of apoptosis was investigated using the
pan-caspase inhibitor Z-Val-Ala-Asp (OMe)-CH 2 F in a murine model of renal I/R. Renal
expression of the chemokines macrophage inflammatory protein-2 (MIP-2) and KC was …
Abstract
Background.
One of the earliest prerequisites for the development of inflammation after ischemia-reperfusion (I/R) is local chemokine expression. We recently demonstrated that apoptosis, characterized by intracellular caspase-activation, contributes to the development of inflammation after I/R.
Methods.
The contribution of apoptosis was investigated using the pan-caspase inhibitor Z-Val-Ala-Asp (OMe)-CH 2 F in a murine model of renal I/R. Renal expression of the chemokines macrophage inflammatory protein-2 (MIP-2) and KC was studied using RT-PCR and immunohistology. Measuring myeloperoxidase activity and serum ureum and creatinine levels assessed neutrophil influx and kidney dysfunction.
Results.
We demonstrate renal up-regulation of KC and MIP-2 after 1 to 16 hr of reperfusion. Treatment with the caspase inhibitor Z-Val-Ala-Asp (OMe)-CH 2 F effectively prevented I/R-induced renal apoptosis, KC, and MIP-2 up-regulation after 2 hr of reperfusion as well as neutrophil influx and functional impairment after 24 hr of reperfusion.
Conclusions.
These data for the first time show that chemokine induction following I/R is dependent on caspase activation.
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