title: Pretreatment with paricalcitol attenuates inflammation in ischemia-reperfusion injury via the up-regulation of cyclooxygenase-2 and prostaglandin E2.
abstract: BACKGROUND
  The effect of paricalcitol on renal ischemia-reperfusion injury (IRI) has not been investigated. We examined whether paricalcitol is effective in preventing inflammation in a mouse model of IRI, and evaluated the cyclooxygenase-2 (COX-2) and prostaglandin E2 (PGE2) pathways as a protective mechanism of paricalcitol.
  
  
  METHODS
  Paricalcitol (0.3 μg/kg) was administered to male C57BL/6 mice 24 h before IRI. Bilateral kidneys were subjected to 23 min of ischemia, and mice were killed 72 h after IRI. The effects of paricalcitol on renal IRI were evaluated in terms of renal function, tubular necrosis, apoptotic cell death, inflammatory cell infiltration and inflammatory cytokines. The effects of paricalcitol on COX-2, PGE2 and its receptors were investigated.
  
  
  RESULTS
  Paricalcitol pretreatment improved renal function (decreased blood urea nitrogen and serum creatinine levels), tubular necrosis and apoptotic cell death in IRI-mice kidneys. The infiltration of inflammatory cells (T cells and macrophages), and the production of proinflammatory cytokines (RANTES, tumor necrosis factor-α, interleukin-1β and interferon-γ) were reduced in paricalcitol-treated mice with IRI. Paricalcitol up-regulated COX-2 expression, PGE2 synthesis and mRNA expression of receptor subtype EP4 in post-ischemic renal tissue. The cotreatment of a selective COX-2 inhibitor with paricalcitol restored functional injury and tubular necrosis in paricalcitol-treated mice with IRI.
  
  
  CONCLUSIONS
  Our study demonstrates that paricalcitol pretreatment prevents renal IRI via the inhibition of renal inflammation, and the up-regulation of COX-2 and PGE2 is one of the protective mechanisms of paricalcitol in renal IRI.
authors.affiliation: Division of Nephrology, Department of Internal Medicine, The Catholic University of Korea, Seoul, Korea.
authors.forename: Hyeon Seok
authors.initials: HS
authors.lastname: Hwang
authors.forename: Keum Jin
authors.initials: KJ
authors.lastname: Yang
authors.forename: Ki Cheol
authors.initials: KC
authors.lastname: Park
authors.forename: Hyun Soo
authors.initials: HS
authors.lastname: Choi
authors.forename: So Hee
authors.initials: SH
authors.lastname: Kim
authors.forename: Sung Youp
authors.initials: SY
authors.lastname: Hong
authors.forename: Byeong Hwa
authors.initials: BH
authors.lastname: Jeon
authors.forename: Yoon Kyung
authors.initials: YK
authors.lastname: Chang
authors.forename: Cheol Whee
authors.initials: CW
authors.lastname: Park
authors.forename: Suk Young
authors.initials: SY
authors.lastname: Kim
authors.forename: Sang Ju
authors.initials: SJ
authors.lastname: Lee
authors.forename: Chul Woo
authors.initials: CW
authors.lastname: Yang
mesh_terms: D000818:Animals; D015153:Blotting, Western; D050071:Bone Density Conservation Agents / Q000494:pharmacology*; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism*; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D015232:Dinoprostone / Q000378:metabolism*; D004195:Disease Models, Animal; D004872:Ergocalciferols / Q000494:pharmacology*; D007124:Immunoenzyme Techniques; D007249:Inflammation / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control*; D007674:Kidney Diseases / Q000150:complications* / Q000188:drug therapy / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D018167:Receptors, Calcitriol / Q000235:genetics / Q000378:metabolism; D015427:Reperfusion Injury / Q000150:complications* / Q000188:drug therapy / Q000473:pathology; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D050071:Bone Density Conservation Agents; D016207:Cytokines; D004872:Ergocalciferols; D012333:RNA, Messenger; D018167:Receptors, Calcitriol; C084656:paricalcitol; D051546:Cyclooxygenase 2; D015232:Dinoprostone