Dataset Information

Paricalcitol attenuates lipopolysaccharide-induced inflammation and apoptosis in proximal tubular cells through the prostaglandin E₂ receptor EP4.

ABSTRACT:

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 E₂ (PGE₂) 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 ?g/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, PGE₂, 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-?B) 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-?B 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-?B signaling after paricalcitol pretreatment in LPS-induced renal proximal tubule cell injury.

SUBMITTER: Hong YA

PROVIDER: S-EPMC5491161 | biostudies-literature | 2017 Jun

REPOSITORIES: biostudies-literature

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Publications

Paricalcitol attenuates lipopolysaccharide-induced inflammation and apoptosis in proximal tubular cells through the prostaglandin E<sub>2</sub> receptor EP4.

Hong Yu Ah YA Yang Keum Jin KJ Jung So Young SY Chang Yoon Kyung YK Park Cheol Whee CW Yang Chul Woo CW Kim Suk Young SY Hwang Hyeon Seok HS

Kidney research and clinical practice 20170630 2

<h4>Background</h4>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<sub>2</sub> (PGE<sub>2</sub>) receptor EP4.<h4>Methods</h4>Human renal tubular epithelial (HK-2) cells were pretreated with paricalcitol (2 ng/m ...[more]

PMID: 28680822

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