Regulation of nitric-oxide synthase mRNA expression by interferon-γ and picolinic acid

Giovanni Melillo, George W. Cox, Arya Biragyn, Lynn A. Sheffler, Luigi Varesio

Research output: Contribution to journalArticle

102 Citations (Scopus)

Abstract

Picolinic acid, a catabolite of L-tryptophan, is a potent co-stimulatory agent for the induction of tumoricidal activity and the production of L- arginine-dependent reactive nitrogen intermediates (RNI) in murine macrophages. We studied whether picolinic acid could affect nitric-oxide synthase (NOS) expression at the gene level in the macrophage cell line ANA- 1. NOS mRNA was neither constitutively expressed nor induced by treatment with picolinic acid alone. However, low levels of NOS mRNA were induced by interferon (IFN)-γ alone. In contrast, a major increase of NOS mRNA expression was observed after treatment with IFN-γ plus picolinic acid. The synergism was already detectable after 5-6 h and increased up to 20 h of treatment. The ability of picolinic acid to augment IFN-γ-dependent NOS mRNA expression was associated with a parallel increase in transcription, as demonstrated by nuclear run-on experiments. Protein synthesis was required for the induction of NOS mRNA because addition of cycloheximide dramatically reduced IFN-γ plus picolinic acid-induced NOS mRNA expression and NOS transcription. These data provide evidence of a molecular event connecting arginine and tryptophan metabolic pathways in the generation of RNI, and they indicate that picolinic acid can induce transcriptional activation of gene expression.

Original languageEnglish
Pages (from-to)8128-8133
Number of pages6
JournalJournal of Biological Chemistry
Volume269
Issue number11
Publication statusPublished - Mar 18 1994

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Nitric Oxide Synthase
Interferons
Messenger RNA
Macrophages
Transcription
Tryptophan
Arginine
Nitrogen
Gene Expression
picolinic acid
Cycloheximide
Metabolic Networks and Pathways
Gene expression
Transcriptional Activation
Genes
Chemical activation
Cells
Cell Line
Proteins

ASJC Scopus subject areas

  • Biochemistry

Cite this

Regulation of nitric-oxide synthase mRNA expression by interferon-γ and picolinic acid. / Melillo, Giovanni; Cox, George W.; Biragyn, Arya; Sheffler, Lynn A.; Varesio, Luigi.

In: Journal of Biological Chemistry, Vol. 269, No. 11, 18.03.1994, p. 8128-8133.

Research output: Contribution to journalArticle

Melillo, G, Cox, GW, Biragyn, A, Sheffler, LA & Varesio, L 1994, 'Regulation of nitric-oxide synthase mRNA expression by interferon-γ and picolinic acid', Journal of Biological Chemistry, vol. 269, no. 11, pp. 8128-8133.
Melillo, Giovanni ; Cox, George W. ; Biragyn, Arya ; Sheffler, Lynn A. ; Varesio, Luigi. / Regulation of nitric-oxide synthase mRNA expression by interferon-γ and picolinic acid. In: Journal of Biological Chemistry. 1994 ; Vol. 269, No. 11. pp. 8128-8133.
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