Abstract | BACKGROUND: METHODS:
Caspase-1-/-, caspase-1+/+ as well as Swiss mice were subjected to 45 min of renal ischemia and 24 hr of reperfusion. Animals were administered agents capable of neutralizing the pro-inflammatory activation products of caspase-1 ( IL-1 receptor antagonist, anti- IL-1 receptor antibody, and anti-IL-18 antibody). The extent of renal functional deterioration, inflammation, and apoptosis were compared. RESULTS: No improvement in renal function as reflected by serum ureum and creatinine were found in caspase-1-/- mice as compared to wild type controls. Caspase-1-/- mice showed slightly attenuated renal inflammation as indicated by decreased renal neutrophil influx, but failed to show changes in intrarenal tumor necrosis factor-alpha production. Moreover, caspase-1-/- mice clearly exhibited reperfusion-induced apoptosis as reflected by renal terminal deoxynucleotidyltransferase histology and internucleosomal DNA cleavage. Treatment with IL-1 receptor antagonist, anti-IL-1 receptor antibody, or anti-IL-18 antibody minimally reduced renal functional deterioration, inflammation, and apoptosis. CONCLUSIONS: These findings suggest that activated caspase-1 and its inflammatory products are involved in, but not crucial to, the induction of inflammation after renal ischemia-reperfusion. Hence, apart from caspase-1, other (combinations of) activated caspases are likely to be more prominently involved in renal reperfusion injury.
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Authors | M A Daemen, G Denecker, C van't Veer, T G Wolfs, P Vandenabeele, W A Buurman |
Journal | Transplantation
(Transplantation)
Vol. 71
Issue 6
Pg. 778-84
(Mar 27 2001)
ISSN: 0041-1337 [Print] United States |
PMID | 11330542
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Inflammation Mediators
- Interleukin-1
- Interleukin-18
- Caspase 1
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Topics |
- Animals
- Apoptosis
(drug effects)
- Caspase 1
(metabolism)
- Enzyme Activation
(physiology)
- Inflammation Mediators
(pharmacology)
- Interleukin-1
(pharmacology)
- Interleukin-18
(pharmacology)
- Kidney
(blood supply, physiology)
- Male
- Mice
- Mice, Inbred C57BL
- Reperfusion Injury
(enzymology, etiology, prevention & control)
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