Paricalcitol attenuates lipopolysaccharide-induced inflammation and apoptosis in proximal tubular cells through the prostaglandin E2 receptor EP4
2017
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
paricalcitolattenuates inflammation and apoptosis during lipopolysaccharide (LPS)-induced renal proximal tubular cell injury through the prostaglandin E2 (PGE2) receptor EP4.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
paricalcitolpretreatment in relation to an EP4 blockade using AH-23848 or EP4 small interfering RNA (siRNA) were investigated.The expression of cyclooxygenase-2, PGE2, and EP4 were significantly increased in LPS-exposed HK-2 cells treated with
paricalcitolcompared with cells exposed to LPS only.
Paricalcitolprevented 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
paricalcitoltreatment. AH-23848 or EP4 siRNA inhibited the suppressive effects of
paricalcitolon 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
paricalcitolin LPS exposed HK-2 cells. The cotreatment with an EP4 antagonist abolished these anti-inflammatory and antiapoptotic effects.EP4 plays a pivotal role in anti-inflammatory and antiapoptotic effects through Akt and NF-κB signaling after
paricalcitolpretreatment in LPS-induced renal proximal tubule cell injury.
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