Increased 5-lipoxygenase activating protein in immune-mediated experimental nerphritis

Angel Montero, Susumu Uda, Uddhav Kelavkar, Ashio Yoshimura, Kamal F. Badr, Karen A. Munger

Research output: Contribution to journalArticlepeer-review

Abstract

Background: The binding of 5-lipoxygenase (5-LO) to 5-LO activating protein (FLAP) is a prerequisite for subsequent formation of leukotrienes from arachidonic acid. Methods: We investigated the localization of FLAP in a rat model of accelerated anti-glomerular basement membrane nephritis and protein expression in cultured rat glomerular endothelial cells. Results: As expected, 5-LO staining was intense and localized exclusively to perinuclear region and inside the nucleus of leukocytes and macrophages. In these cells, FLAP immunoreactivity co-localized with that of 5-LO, and was restricted to nuclear envelope. Surprisingly, intense nuclear and cytoplasmic staining for FLAP was also observed in glomerular endothelial cells in early experimental glomerulonephritis. Although 5-LO and FLAP mRNA were detected in cultured rat glomerular endothelial cells by RT-PCR, Western blot revealed only FLAP and no 5-LO protein. FLAP protein was regulated in glomerular endothelial cells by the proinflammatory cytokine, interferon-γ, in a dose-dependent manner. Conclusion: The unexpected discovery of FLAP in glomerular endothelial cells in this model of glomerulonephritis, coupled with our demonstration that oral FLAP antagonist therapy reduces proteinuria in human glomerulonephritis and animal models of diabetes, provides further impetus to examine the role of this pro-inflammatory protein in glomerular immune injury.

Original languageEnglish (US)
Pages (from-to)682-690
Number of pages9
JournalJournal of Nephrology
Volume16
Issue number5
StatePublished - Sep 2003
Externally publishedYes

Keywords

  • Five-lipoxygenase activating protein
  • Glomerular endothelial cells
  • Glomerulonephritis

ASJC Scopus subject areas

  • Nephrology

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