Naslov
The Inflammasome in Cisplatin-Induced AKI

Autori
Hyun-Jung Kim ; Dong Won Lee ; Zhibin He ; Galešić Ljubanović, Danica ; Charles L. Edelstein,

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni

Skup
American Society of Nephrology (ASN) Kidney Week

Mjesto i datum
San Diego (CA), Sjedinjene Američke Države, 30.10.2012. - 04.11.2012

Vrsta sudjelovanja
Poster

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
Inflammasome; Cisplatin-Induced AKI

Sažetak
Background: We have demonstrated that there is increased caspase-1, IL-1α, IL-1β and IL-18 in cisplatin (Cis)-induced AKI (CIA). As IL-1α, IL-1β and IL-18 are activated by caspase-1 in the inflammasome, the aim of the study was to further investigate the inflammasome in CIA. The NALP3 inflammasomes is a cytosolic complex consisting NALP3 protein, ASC protein and caspase-5. BID is a pro-apoptotic protein that is secreted by the inflammasome. Methods: Mice were injected with Cis (25 mg/kg) and developed AKI on day 3. ATN was graded as to the number of tubules with histological features of ATN. Results: On immunoblot of whole kidney, there were a 1.3-fold increase in NALP3 on day 2 (P=0.05, n=9) and a 2.6-fold increase in NALP1 (P<0.05, n=9) on day 3 of CIA. On immunoblot, there were a 2-fold increase in ASC on day 2 (P<0.05, n=10), a 3-fold increase in caspase-5 protein on day 2 (P<0.05, n=10), a 2-fold increase in BID on day 2 (P<0.05, n=10), and a 1.2-fold increase in caspase-1 (P<0.05, n=9). As the increase in NALP3 occurred on day 2 at the same time as the increase in ASC, caspase-5, BID and caspase-1, and before the AKI, we considered that inhibition of NALP3 may play an injurious role. To determine whether the increase in NALP3 plays an injurious role in CIA, NALP3-/- mice were studied. Serum creatinine (mg/dL) was 0.22 in vehicle (Veh)-treated, 2.0 in Cis-treated wild type (P< 0.001 vs. Veh, n=10) and 1.2 in Cis- treated NALP3-/- mice (NS vs. wild type, n=9). BUN (mg/dL) was 23 in Veh-treated, 209 in Cis-treated wild type (P< 0.001 vs. Veh, n=10) and 201 in Cis- treated NALP3-/- mice (NS vs. wild type, n=9). ATN score was 1.8 in Cis-treated wild type and 1.5 in Cis-treated NALP3-/- mice (NS vs. wild type, n=5). Apoptosis score (apoptotic cells per 10 HPF) was 8.4 in Cis-treated wild type and 1.4 in Cis- treated NALP3-/- mice (NS vs. wild type, n=5). Conclusions: Inflammasome proteins NALP3, caspase- 1, caspase-5, ASC and BID are increased in whole kidneys on day 2 of CIA. However, NALP3-/- mice are not functionally or histologically protected suggesting that the NALP3 inflammasome does not play an injurious role in CIA. Further investigation of the NALP1 imflammasome is warranted.

Izvorni jezik
Engleski

Znanstvena područja
Kliničke medicinske znanosti

POVEZANOST RADA