title: Renoprotective effect of paricalcitol via a modulation of the TLR4-NF-κB pathway in ischemia/reperfusion-induced acute kidney injury.
abstract: BACKGROUND
  The pathophysiology of ischemic acute kidney injury (AKI) is thought to include a complex interplay between vascular endothelial cell dysfunction, inflammation, and tubular cell damage. Several lines of evidence suggest a potential anti-inflammatory effect of vitamin D in various kidney injury models. In this study, we investigated the effect of paricalcitol, a synthetic vitamin D analog, on renal inflammation in a mouse model of ischemia/reperfusion (I/R) induced acute kidney injury (AKI).
  
  
  METHODS
  Paricalcitol was administered via intraperitoneal (IP) injection at 24h before ischemia, and then I/R was performed through bilateral clamping of the renal pedicles. Twenty-four hours after I/R, mice were sacrificed for the evaluation of injury and inflammation. Additionally, an in vitro experiment using HK-2 cells was also performed to examine the direct effect of paricalcitol on tubular cells.
  
  
  RESULTS
  Pre-treatment with paricalcitol attenuated functional deterioration and histological damage in I/R induced AKI, and significantly decreased tissue neutrophil and macrophage infiltration and the levels of chemokines, the pro-inflammatory cytokine interleukin-6 (IL-6), and monocyte chemoattractant protein-1 (MCP-1). It also decreased IR-induced upregulation of Toll-like receptor 4 (TLR4), and nuclear translocation of p65 subunit of NF-κB. Results from the in vitro study showed pre-treatment with paricalcitol suppressed the TNF-α-induced depletion of cytosolic IκB in HK-2 cells.
  
  
  CONCLUSIONS
  These results demonstrate that pre-treatment with paricalcitol has a renoprotective effect in ischemic AKI, possibly by suppressing TLR4-NF-κB mediated inflammation.
authors.affiliation: Division of Nephrology, Department of Internal Medicine, Korea University Medical College, Seoul, Republic of Korea. Electronic address: maestro97@hanmail.net.
authors.forename: Jae-Won
authors.initials: JW
authors.lastname: Lee
authors.affiliation: Division of Nephrology, Department of Internal Medicine, Korea University Medical College, Seoul, Republic of Korea. Electronic address: linefe99@hanmail.net.
authors.forename: Sun Chul
authors.initials: SC
authors.lastname: Kim
authors.affiliation: Division of Nephrology, Department of Internal Medicine, Korea University Medical College, Seoul, Republic of Korea. Electronic address: rainboweyes@hanmail.net.
authors.forename: Yoon Sook
authors.initials: YS
authors.lastname: Ko
authors.affiliation: Division of Nephrology, Department of Internal Medicine, Korea University Medical College, Seoul, Republic of Korea. Electronic address: cell1023@hanmail.net.
authors.forename: Hee Young
authors.initials: HY
authors.lastname: Lee
authors.affiliation: Division of Nephrology, Department of Internal Medicine, Korea University Medical College, Seoul, Republic of Korea. Electronic address: icdej@naver.com.
authors.forename: Eunjung
authors.initials: E
authors.lastname: Cho
authors.affiliation: Division of Nephrology, Department of Internal Medicine, Korea University Medical College, Seoul, Republic of Korea. Electronic address: gyu219@hanmail.net.
authors.forename: Myung-Gyu
authors.initials: MG
authors.lastname: Kim
authors.affiliation: Division of Nephrology, Department of Internal Medicine, Korea University Medical College, Seoul, Republic of Korea. Electronic address: sang-kyung@korea.ac.kr.
authors.forename: Sang-Kyung
authors.initials: SK
authors.lastname: Jo
authors.affiliation: Division of Nephrology, Department of Internal Medicine, Korea University Medical College, Seoul, Republic of Korea. Electronic address: wonyong@korea.ac.kr.
authors.forename: Won Yong
authors.initials: WY
authors.lastname: Cho
authors.affiliation: Division of Nephrology, Department of Internal Medicine, Korea University Medical College, Seoul, Republic of Korea. Electronic address: hyoung@korea.ac.kr.
authors.forename: Hyoung Kyu
authors.initials: HK
authors.lastname: Kim
mesh_terms: D058186:Acute Kidney Injury / Q000097:blood / Q000209:etiology / Q000378:metabolism*; D000818:Animals; D015153:Blotting, Western; D002460:Cell Line; D018932:Chemokine CCL2 / Q000378:metabolism; D018925:Chemokines / Q000378:metabolism; D003401:Creatine / Q000097:blood; D004872:Ergocalciferols / Q000494:pharmacology*; D006801:Humans; D051550:I-kappa B Kinase / Q000378:metabolism; D007249:Inflammation / Q000097:blood / Q000209:etiology / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D007668:Kidney / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008264:Macrophages / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009504:Neutrophils / Q000378:metabolism / Q000473:pathology; D015427:Reperfusion Injury / Q000150:complications; D015398:Signal Transduction / Q000187:drug effects*; D051197:Toll-Like Receptor 4 / Q000378:metabolism*; D051996:Transcription Factor RelA / Q000378:metabolism*
chemical_list: C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D018925:Chemokines; D004872:Ergocalciferols; D015850:Interleukin-6; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4; D051996:Transcription Factor RelA; C084656:paricalcitol; D051550:I-kappa B Kinase; D003401:Creatine
keywords: Acute kidney injury; NF-κB; Paricalcitol; Toll-like receptor 4