Cyclosporine decreases prostaglandin E2 production in mouse medullary thick ascending limb cultured cells

Chiz Tzung Chang, Cheng Chieh Hung, Chih Wei Yang, Alain Vandewalle, Mai Szu Wu

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

Intrarenal vasoconstriction is thought to be the major pathogenesis of cyclosporine (CsA) nephrotoxicity. Nitric oxide (NO) and prostaglandin E2 (PGE2) are two of the major intrarenal vasodilators, which protect kidney from ischemia. CsA inhibited NO production in renal epithelial cells. The interaction between CsA and intrarenal PGE2 and NO production is still unclear. The aim of the study is to evaluate the interaction of CsA with intrarenal PGE2 and NO production in renal epithelial cells. Models of cultured mouse thick ascending limb (TAL) cells are chosen to perform the experiments, as TAL cells are the major site of intrarenal PGE2 production and target of CsA nephrotoxicity. We investigated the PGE2 production by enzyme-linked immunosorbent assay, and cyclooxygenase (COX-1 and COX-2) mRNA expression by RT-PCR in cultured cells treated with or without CsA. TAL cells maintained the main characteristics of their parental cells. TAL cells produce PGE2 mainly by COX-1 in steady state and by COX-2 in stimulated state by lipopolysaccharide (LPS). CsA (100 ng/ml) significantly reduced the PGE2 production up to 43% in TAL cells in LPS stimulated status (control versus CsA: 375.1 ± 15.5 vs. 187.2 ± 12.2 nM/ mg protein, n = 7, P <0.001). The effects were dose-dependent. The mRNA expression of COX-1 is not affected and COX-2 is decreased in CsA-treated TAL cells. NO donor could prevent the inhibitory effects of CsA. We concluded that CsA decreased intrarenal PGE2 production in stimulated status mainly by decreasing COX-2 expression. NO might play a role in the CsA effect. The results suggested the role possible of PGE2 in CsA nephrotoxicity.

Original languageEnglish
Pages (from-to)871-878
Number of pages8
JournalTransplant International
Volume18
Issue number7
DOIs
Publication statusPublished - Jul 2005
Externally publishedYes

Keywords

  • Cyclooxygenase 2
  • Cyclosporine
  • Medullary thick ascending limb
  • Nitric oxide
  • Prostaglandin E2

ASJC Scopus subject areas

  • Transplantation

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