PMID- 24434153 OWN - NLM STAT- MEDLINE DCOM- 20140430 LR - 20141120 IS - 1090-2104 (Electronic) IS - 0006-291X (Linking) VI - 444 IP - 2 DP - 2014 Feb 7 TI - Renoprotective effect of paricalcitol via a modulation of the TLR4-NF-kappaB pathway in ischemia/reperfusion-induced acute kidney injury. PG - 121-7 LID - S0006-291X(14)00020-5 [pii] LID - 10.1016/j.bbrc.2014.01.005 [doi] AB - 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-kappaB. Results from the in vitro study showed pre-treatment with paricalcitol suppressed the TNF-alpha-induced depletion of cytosolic IkappaB in HK-2 cells. CONCLUSION: These results demonstrate that pre-treatment with paricalcitol has a renoprotective effect in ischemic AKI, possibly by suppressing TLR4-NF-kappaB mediated inflammation. CI - Copyright (c) 2014. Published by Elsevier Inc. FAU - Lee, Jae-Won AU - Lee JW AD - Division of Nephrology, Department of Internal Medicine, Korea University Medical College, Seoul, Republic of Korea. Electronic address: maestro97@hanmail.net. FAU - Kim, Sun Chul AU - Kim SC AD - Division of Nephrology, Department of Internal Medicine, Korea University Medical College, Seoul, Republic of Korea. Electronic address: linefe99@hanmail.net. FAU - Ko, Yoon Sook AU - Ko YS AD - Division of Nephrology, Department of Internal Medicine, Korea University Medical College, Seoul, Republic of Korea. Electronic address: rainboweyes@hanmail.net. FAU - Lee, Hee Young AU - Lee HY AD - Division of Nephrology, Department of Internal Medicine, Korea University Medical College, Seoul, Republic of Korea. Electronic address: cell1023@hanmail.net. FAU - Cho, Eunjung AU - Cho E AD - Division of Nephrology, Department of Internal Medicine, Korea University Medical College, Seoul, Republic of Korea. Electronic address: icdej@naver.com. FAU - Kim, Myung-Gyu AU - Kim MG AD - Division of Nephrology, Department of Internal Medicine, Korea University Medical College, Seoul, Republic of Korea. Electronic address: gyu219@hanmail.net. FAU - Jo, Sang-Kyung AU - Jo SK AD - Division of Nephrology, Department of Internal Medicine, Korea University Medical College, Seoul, Republic of Korea. Electronic address: sang-kyung@korea.ac.kr. FAU - Cho, Won Yong AU - Cho WY AD - Division of Nephrology, Department of Internal Medicine, Korea University Medical College, Seoul, Republic of Korea. Electronic address: wonyong@korea.ac.kr. FAU - Kim, Hyoung Kyu AU - Kim HK AD - Division of Nephrology, Department of Internal Medicine, Korea University Medical College, Seoul, Republic of Korea. Electronic address: hyoung@korea.ac.kr. LA - eng PT - Journal Article DEP - 20140114 PL - United States TA - Biochem Biophys Res Commun JT - Biochemical and biophysical research communications JID - 0372516 RN - 0 (Ccl2 protein, mouse) RN - 0 (Chemokine CCL2) RN - 0 (Chemokines) RN - 0 (Ergocalciferols) RN - 0 (Interleukin-6) RN - 0 (Tlr4 protein, mouse) RN - 0 (Toll-Like Receptor 4) RN - 0 (Transcription Factor RelA) RN - 6702D36OG5 (paricalcitol) RN - EC 2.7.11.10 (I-kappa B Kinase) RN - MU72812GK0 (Creatine) SB - IM MH - Acute Kidney Injury/blood/etiology/*metabolism MH - Animals MH - Blotting, Western MH - Cell Line MH - Chemokine CCL2/metabolism MH - Chemokines/metabolism MH - Creatine/blood MH - Ergocalciferols/*pharmacology MH - Humans MH - I-kappa B Kinase/metabolism MH - Inflammation/blood/etiology/metabolism MH - Interleukin-6/metabolism MH - Kidney/drug effects/metabolism/pathology MH - Macrophages/metabolism/pathology MH - Male MH - Mice MH - Mice, Inbred C57BL MH - Neutrophils/metabolism/pathology MH - Reperfusion Injury/complications MH - Signal Transduction/*drug effects MH - Toll-Like Receptor 4/*metabolism MH - Transcription Factor RelA/*metabolism OTO - NOTNLM OT - Acute kidney injury OT - NF-kappaB OT - Paricalcitol OT - Toll-like receptor 4 EDAT- 2014/01/18 06:00 MHDA- 2014/05/03 06:00 CRDT- 2014/01/18 06:00 PHST- 2013/12/24 00:00 [received] PHST- 2014/01/07 00:00 [accepted] PHST- 2014/01/18 06:00 [entrez] PHST- 2014/01/18 06:00 [pubmed] PHST- 2014/05/03 06:00 [medline] AID - S0006-291X(14)00020-5 [pii] AID - 10.1016/j.bbrc.2014.01.005 [doi] PST - ppublish SO - Biochem Biophys Res Commun. 2014 Feb 7;444(2):121-7. doi: 10.1016/j.bbrc.2014.01.005. Epub 2014 Jan 14.