Exogenous interferon-gamma induces endogenous synthesis of interferon-alpha and -beta by murine macrophages for induction of nitric oxide synthase.
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.
Zhou
A
A
Oklahoma Medical Research Foundation, Noble Center for Biomedical Research, Oklahoma City 73104-5046, USA.
Chen
Z
Z
Rummage
J A
JA
Jiang
H
H
Kolosov
M
M
Kolosova
I
I
Stewart
C A
CA
Leu
R W
RW
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D001483:Base Sequence; D004790:Enzyme Induction; D004797:Enzyme-Linked Immunosorbent Assay; D007369:Interferon Inducers / Q000494:pharmacology*; D007370:Interferon Type I / Q000096:biosynthesis* / Q000378:metabolism; D007939:Leukemia L1210 / Q000188:drug therapy / Q000473:pathology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects* / Q000201:enzymology; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D008969:Molecular Sequence Data; D019001:Nitric Oxide Synthase / Q000096:biosynthesis*; D016133:Polymerase Chain Reaction; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D007369:Interferon Inducers; D007370:Interferon Type I; D008070:Lipopolysaccharides; D019001:Nitric Oxide Synthase