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Paricalcitol attenuates lipopolysaccharide-induced inflammation and apoptosis in proximal tubular cells through the prostaglandin E(2) receptor EP4

BACKGROUND: Vitamin D is considered to exert a protective effect on various renal diseases but its underlying molecular mechanism remains poorly understood. This study aimed to determine whether paricalcitol attenuates inflammation and apoptosis during lipopolysaccharide (LPS)-induced renal proximal...

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Autores principales: Hong, Yu Ah, Yang, Keum Jin, Jung, So Young, Chang, Yoon Kyung, Park, Cheol Whee, Yang, Chul Woo, Kim, Suk Young, Hwang, Hyeon Seok
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Korean Society of Nephrology 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5491161/
https://www.ncbi.nlm.nih.gov/pubmed/28680822
http://dx.doi.org/10.23876/j.krcp.2017.36.2.145
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author Hong, Yu Ah
Yang, Keum Jin
Jung, So Young
Chang, Yoon Kyung
Park, Cheol Whee
Yang, Chul Woo
Kim, Suk Young
Hwang, Hyeon Seok
author_facet Hong, Yu Ah
Yang, Keum Jin
Jung, So Young
Chang, Yoon Kyung
Park, Cheol Whee
Yang, Chul Woo
Kim, Suk Young
Hwang, Hyeon Seok
author_sort Hong, Yu Ah
collection PubMed
description BACKGROUND: Vitamin D is considered to exert a protective effect on various renal diseases but its underlying molecular mechanism remains poorly understood. This study aimed to determine whether paricalcitol attenuates inflammation and apoptosis during lipopolysaccharide (LPS)-induced renal proximal tubular cell injury through the prostaglandin E(2) (PGE(2)) receptor EP4. METHODS: Human renal tubular epithelial (HK-2) cells were pretreated with paricalcitol (2 ng/mL) for 1 hour and exposed to LPS (1 μg/mL). The effects of paricalcitol pretreatment in relation to an EP4 blockade using AH-23848 or EP4 small interfering RNA (siRNA) were investigated. RESULTS: The expression of cyclooxygenase-2, PGE(2), and EP4 were significantly increased in LPS-exposed HK-2 cells treated with paricalcitol compared with cells exposed to LPS only. Paricalcitol prevented cell death induced by LPS exposure, and the cotreatment of AH-23848 or EP4 siRNA offset these cell-protective effects. The phosphorylation and nuclear translocation of p65 nuclear factor-kappaB (NF-κB) were decreased and the phosphorylation of Akt was increased in LPS-exposed cells with paricalcitol treatment. AH-23848 or EP4 siRNA inhibited the suppressive effects of paricalcitol on p65 NF-κB nuclear translocation and the activation of Akt. The production of proinflammatory cytokines and the number of terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling-positive cells were attenuated by paricalcitol in LPS exposed HK-2 cells. The cotreatment with an EP4 antagonist abolished these anti-inflammatory and antiapoptotic effects. CONCLUSION: EP4 plays a pivotal role in anti-inflammatory and antiapoptotic effects through Akt and NF-κB signaling after paricalcitol pretreatment in LPS-induced renal proximal tubule cell injury.
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spelling pubmed-54911612017-07-05 Paricalcitol attenuates lipopolysaccharide-induced inflammation and apoptosis in proximal tubular cells through the prostaglandin E(2) receptor EP4 Hong, Yu Ah Yang, Keum Jin Jung, So Young Chang, Yoon Kyung Park, Cheol Whee Yang, Chul Woo Kim, Suk Young Hwang, Hyeon Seok Kidney Res Clin Pract Original Article BACKGROUND: Vitamin D is considered to exert a protective effect on various renal diseases but its underlying molecular mechanism remains poorly understood. This study aimed to determine whether paricalcitol attenuates inflammation and apoptosis during lipopolysaccharide (LPS)-induced renal proximal tubular cell injury through the prostaglandin E(2) (PGE(2)) receptor EP4. METHODS: Human renal tubular epithelial (HK-2) cells were pretreated with paricalcitol (2 ng/mL) for 1 hour and exposed to LPS (1 μg/mL). The effects of paricalcitol pretreatment in relation to an EP4 blockade using AH-23848 or EP4 small interfering RNA (siRNA) were investigated. RESULTS: The expression of cyclooxygenase-2, PGE(2), and EP4 were significantly increased in LPS-exposed HK-2 cells treated with paricalcitol compared with cells exposed to LPS only. Paricalcitol prevented cell death induced by LPS exposure, and the cotreatment of AH-23848 or EP4 siRNA offset these cell-protective effects. The phosphorylation and nuclear translocation of p65 nuclear factor-kappaB (NF-κB) were decreased and the phosphorylation of Akt was increased in LPS-exposed cells with paricalcitol treatment. AH-23848 or EP4 siRNA inhibited the suppressive effects of paricalcitol on p65 NF-κB nuclear translocation and the activation of Akt. The production of proinflammatory cytokines and the number of terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling-positive cells were attenuated by paricalcitol in LPS exposed HK-2 cells. The cotreatment with an EP4 antagonist abolished these anti-inflammatory and antiapoptotic effects. CONCLUSION: EP4 plays a pivotal role in anti-inflammatory and antiapoptotic effects through Akt and NF-κB signaling after paricalcitol pretreatment in LPS-induced renal proximal tubule cell injury. Korean Society of Nephrology 2017-06 2017-06-30 /pmc/articles/PMC5491161/ /pubmed/28680822 http://dx.doi.org/10.23876/j.krcp.2017.36.2.145 Text en Copyright © 2017 by The Korean Society of Nephrology This is an open-access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Article
Hong, Yu Ah
Yang, Keum Jin
Jung, So Young
Chang, Yoon Kyung
Park, Cheol Whee
Yang, Chul Woo
Kim, Suk Young
Hwang, Hyeon Seok
Paricalcitol attenuates lipopolysaccharide-induced inflammation and apoptosis in proximal tubular cells through the prostaglandin E(2) receptor EP4
title Paricalcitol attenuates lipopolysaccharide-induced inflammation and apoptosis in proximal tubular cells through the prostaglandin E(2) receptor EP4
title_full Paricalcitol attenuates lipopolysaccharide-induced inflammation and apoptosis in proximal tubular cells through the prostaglandin E(2) receptor EP4
title_fullStr Paricalcitol attenuates lipopolysaccharide-induced inflammation and apoptosis in proximal tubular cells through the prostaglandin E(2) receptor EP4
title_full_unstemmed Paricalcitol attenuates lipopolysaccharide-induced inflammation and apoptosis in proximal tubular cells through the prostaglandin E(2) receptor EP4
title_short Paricalcitol attenuates lipopolysaccharide-induced inflammation and apoptosis in proximal tubular cells through the prostaglandin E(2) receptor EP4
title_sort paricalcitol attenuates lipopolysaccharide-induced inflammation and apoptosis in proximal tubular cells through the prostaglandin e(2) receptor ep4
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5491161/
https://www.ncbi.nlm.nih.gov/pubmed/28680822
http://dx.doi.org/10.23876/j.krcp.2017.36.2.145
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