Modulation of inflammatory response by selective inhibition of cyclooxygenase-1 and cyclooxygenase-2 in acute kidney injury.
OBJECTIVE
This work explored the role of inhibition of cyclooxygenases (COXs) in modulating the inflammatory response triggered by acute kidney injury.


METHODS
C57Bl/6 mice were used.


METHODS
Animals were treated or not with indomethacin (IMT) prior to injury (days -1 and 0).


METHODS
Animals were subjected to 45 min of renal pedicle occlusion and sacrificed at 24 h after reperfusion. Serum creatinine and blood urea nitrogen, reactive oxygen species (ROS), kidney myeloperoxidase (MPO) activity, and prostaglandin E2 (PGE(2)) levels were analyzed. Tumor necrosis factor (TNF)-alpha, t-bet, interleukin (IL)-10, IL-1beta, heme oxygenase (HO)-1, and prostaglandin E synthase (PGES) messenger RNA (mRNA) were studied. Cytokines were quantified in serum.


RESULTS
IMT-treated animals presented better renal function with less acute tubular necrosis and reduced ROS and MPO production. Moreover, the treatment was associated with lower expression of TNF-alpha, PGE(2), PGES, and t-bet and upregulation of HO-1 and IL-10. This profile was mirrored in serum, where inhibition of COXs significantly decreased interferon (IFN)-gamma, TNF-alpha, and IL-12 p70 and upregulated IL-10.


CONCLUSIONS
COXs seem to play an important role in renal ischemia and reperfusion injury, involving the secretion of pro-inflammatory cytokines, activation of neutrophils, and ROS production. Inhibition of COX pathway is intrinsically involved with cytoprotection.
Feitoza
Carla Q
CQ
Laboratory of Experimental and Clinical Immunology, Nephrology Division, Federal University of São Paulo, São Paulo, Brazil.
Semedo
Patricia
P
Gonçalves
Giselle M
GM
Cenedeze
Marcos A
MA
Pinheiro
Hélady S
HS
Dos Santos
Oscar Fernando Pavão
OF
Landgraf
Richardt Gama
RG
Pacheco-Silva
Alvaro
A
Câmara
Niels Olsen Saraiva
NO
D058186:Acute Kidney Injury / Q000378:metabolism*; D000818:Animals; D051545:Cyclooxygenase 1 / Q000378:metabolism*; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D016207:Cytokines / Q000097:blood; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D007213:Indomethacin / Q000494:pharmacology*; D007249:Inflammation / Q000378:metabolism*; D016753:Interleukin-10 / Q000378:metabolism; D007668:Kidney / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009195:Peroxidase / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D015427:Reperfusion Injury / Q000378:metabolism
D016861:Cyclooxygenase Inhibitors; D016207:Cytokines; D017382:Reactive Oxygen Species; D016753:Interleukin-10; D009195:Peroxidase; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D007213:Indomethacin