Augmentation of nitric oxide production by gamma interferon in a mouse vascular endothelial cell line and its modulation by tumor necrosis factor alpha and lipopolysaccharide

A. Morikawa, N. Koide, Y. Kato, T. Sugiyama, D. Chakravortty, T. Yoshida, T. Yokochi

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49 Citations (Scopus)

Abstract

The effect of gamma interferon (IFN-γ), tumor necrosis factor alpha (TNF-α), and lipopolysaccharide (LPS) on nitric oxide (NO) production in the mouse vascular aortic endothelial cell line END-D was examined. LPS, TNF-α, and a low concentration of IFN-γ inhibited NO production in END-D cells, while a high concentration of IFN-γ definitely enhanced it. The NO production induced by a high concentration of IFN-γ was further augmented by using IFN-γ in combination with LPS or TNF-α. In sequential incubations of LPS and IFN-γ, the enhancement of NO production required prior treatment with IFN-γ. Stimulation of END-D cells with a high concentration of IFN-γ led to the expression of inducible NO synthase (iNOS). The augmentation of NO production by IFN-γ alone or in combination with LPS or TNF-α was completely blocked by several inhibitors of iNOS. It was strongly suggested that a high concentration of IFN-γ itself enhanced NO production in END-D cells through inducing the expression of iNOS. LPS and TNF-α exclusively modulated the activity of iNOS once its expression was triggered by IFN-γ. On the other hand, a low concentration of IFN-γ LPS, and TNF-α reduced NO production through down-regulating constitutive NOS (cNOS). The differential regulation of cNOS- and iNOS-mediated NO production by IFN-γ TNF-α, and LPS is discussed.

Original languageEnglish
Pages (from-to)6209-6214
Number of pages6
JournalInfection and Immunity
Volume68
Issue number11
DOIs
Publication statusPublished - 2000
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Parasitology
  • Microbiology
  • Immunology
  • Infectious Diseases

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