title: Modulation of inflammatory response by selective inhibition of cyclooxygenase-1 and cyclooxygenase-2 in acute kidney injury.
abstract: 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.
authors.affiliation: Laboratory of Experimental and Clinical Immunology, Nephrology Division, Federal University of São Paulo, São Paulo, Brazil.
authors.forename: Carla Q
authors.initials: CQ
authors.lastname: Feitoza
authors.forename: Patricia
authors.initials: P
authors.lastname: Semedo
authors.forename: Giselle M
authors.initials: GM
authors.lastname: Gonçalves
authors.forename: Marcos A
authors.initials: MA
authors.lastname: Cenedeze
authors.forename: Hélady S
authors.initials: HS
authors.lastname: Pinheiro
authors.forename: Oscar Fernando Pavão
authors.initials: OF
authors.lastname: Dos Santos
authors.forename: Richardt Gama
authors.initials: RG
authors.lastname: Landgraf
authors.forename: Alvaro
authors.initials: A
authors.lastname: Pacheco-Silva
authors.forename: Niels Olsen Saraiva
authors.initials: NO
authors.lastname: Câmara
mesh_terms: 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
chemical_list: D016861:Cyclooxygenase Inhibitors; D016207:Cytokines; D017382:Reactive Oxygen Species; D016753:Interleukin-10; D009195:Peroxidase; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D007213:Indomethacin