Leukotrienes do not regulate nitric oxide production in RAW 264.7 macrophages

Academic Article

Abstract

  • RAW 264.7 macrophages respond to lipopolysaccharide (LPS) and interferon-γ (IFN-γ) by producing large amounts of nitric oxide (NO) and prostaglandin E2 (PGE2), with maximal production 18-24 h after treatment. Following stimulation with the calcium inophore A23187, cultures of RAW cells also produce modest amounts of leukotrienes. However, the capacity of these cells to produce leukotrienes is transient, beginning 2 h after vehicle or LPS/IFN-γ treatment, peaking by 4-6 h and absent by 8 h. A-79175, (R (+) N-[3-[5-(4-Fluorophenoxy)-2-furanyl]-1-methyl-2-propynyl]-N-hydroxyurea) a specific inhibitor of 5-lipoxygenase (5-LO), abolished leukotriene production by RAW cells in a dose-dependent, non-cytotoxic fashion while having no effect on PGE2 or NO production. By contrast, nordihydroguaiaretic acid (NDGA) inhibited production of leukotrienes, PGE2 and NO only at doses that were cytotoxic to the RAW cells. Exogenous leukotriene B4 (LTB4) had no effect on either NO or PGE2 production. An inhibitor of NO production, L-N-5-(1-iminoethyl) ornithine HCl (NIO) also did not affect leukotriene or PGE2 production, while dexamethasone blocked PGE2 and NO production, but did not affect leukotriene production in these cells. Taken collectively, these results indicate that there is no interaction between the pathways for leukotriene and nitric oxide production in RAW 264.7 macrophages.
  • Digital Object Identifier (doi)

    Author List

  • Hulkower KI; Pollock JS; Walsh RE; Huang R; Otis ER; Brooks CDW; Bell RL
  • Start Page

  • 145
  • End Page

  • 149
  • Volume

  • 55
  • Issue

  • 3