Exogenous interferon-gamma induces endogenous synthesis of interferon-alpha and -beta by murine macrophages for induction of nitric oxide synthase

• Published in: Journal of interferon & cytokine research Vol. 15; no. 10; p. 897
• Main Authors: Zhou, A, Chen, Z, Rummage, J A, Jiang, H, Kolosov, M, Kolosova, I, Stewart, C A, Leu, R W
• Format: Journal Article
• Language: English
• Published: United States 01-10-1995
• Subjects: Animals; Antineoplastic Agents - pharmacology; Base Sequence; Enzyme Induction; Enzyme-Linked Immunosorbent Assay; Interferon Inducers - pharmacology; Interferon Type I - biosynthesis; Interferon Type I - secretion; Leukemia L1210 - drug therapy; Leukemia L1210 - pathology; Lipopolysaccharides - pharmacology; Macrophages - drug effects; Macrophages - enzymology; Male; Mice; Mice, Inbred C3H; Molecular Sequence Data; Nitric Oxide Synthase - biosynthesis; Polymerase Chain Reaction; Transcription, Genetic; Tumor Cells, Cultured
• ISSN: 1079-9907
• DOI: 10.1089/jir.1995.15.897

Murine macrophages (M phi) are activated either by interferon-gamma (IFN-gamma) or interferon-alpha/beta (IFN-alpha/beta) in combination with bacterial lipopolysaccharide (LPS) to induce synthesis of tumor necrosis factor alpha (TNF-alpha) and nitric oxide synthase (iNOS) mRNA synthesis for generation of tumor cytotoxic nitric oxide (NO). In the present study, the effect of exogenous IFN-gamma on the induction of endogenous mRNA synthesis and secretion of IFN-alpha/beta by murine M phi was investigated. Neutralizing antibodies to IFN-alpha/beta reversed TNF-alpha and NOS mRNA synthesis, as well as nitric oxide (NO)-mediated tumor cytotoxicity. Quantitative reverse transcription polymerase chain reaction (RT-PCR) revealed that treatment of M phi with IFN-gamma induced increases in both IFN-alpha and IFN-beta mRNA synthesis by approximately 2-fold and 10-fold, respectively, which corresponded to a 2-fold increase in secretion of IFN-alpha/beta by ELISA. These data indicate that exogenous IFN-gamma induces endogenous synthesis and secretion of IFN-alpha/beta by M phi, which appears to act in concert with endogenously synthesized TNF-alpha for the autocrine induction of NOS mRNA synthesis.