14602203

pubmed:Citation

2

Infection of J774.1 murine macrophages by influenza A virus (IAV) induces two major responses, production of host defense molecules and death by apoptosis. We investigated whether induction of two cytotoxic compounds, tumor necrosis factor-alpha (TNF-alpha) and nitric oxide (NO), directly caused IAV-induced apoptosis, and whether induction could be modulated by interferon-gamma (IFN-gamma) or the replication competence of the virus. Live IAV potently induced production of both TNF-alpha and NO, but UV inactivated virus was a poor inducer of both molecules. When cells were pre-treated with IFN-gamma, inactive IAV became as effective an inducer of NO, but not TNF-alpha, as live IAV. Amantadine, which antagonizes viral entry and replication, partly inhibited TNF-alpha and NO production in unprimed cells, but did not inhibit NO in IFN-gamma primed cells. IAV-induced cytotoxicity was not due to the induction of TNF-alpha or NO. Cells were insensitive to either TNF-alpha-containing supernatants or to recombinant TNF-alpha. Anti-TNF-alpha antibody did not protect cells from IAV-induced cell death, and anti-oxidants that inhibited TNF-alpha production also failed to increase cell survival. Inhibitors of NO production did not protect from IAV-induced cell death, either alone or in combination with superoxide dismutase (SOD). We conclude that, even though IAV was a potent inducer of TNF-alpha and NO in macrophages, IAV-induced apoptosis was not mediated directly by them. Importantly, viral replication was not required for the induction of TNF-alpha or NO, and the action of inactive IAV could be potentiated by IFN-gamma.

eng

IM

MEDLINE

0168-1702

Print

NLM

117-26

pubmed-meshheading:14602203-Amantadine, pubmed-meshheading:14602203-Animals, pubmed-meshheading:14602203-Antibodies, pubmed-meshheading:14602203-Antioxidants, pubmed-meshheading:14602203-Antiviral Agents, pubmed-meshheading:14602203-Apoptosis, pubmed-meshheading:14602203-Cell Line, pubmed-meshheading:14602203-Culture Media, Conditioned, pubmed-meshheading:14602203-Influenza A virus, pubmed-meshheading:14602203-Interferon-gamma, pubmed-meshheading:14602203-Macrophages, pubmed-meshheading:14602203-Mice, pubmed-meshheading:14602203-Nitric Oxide, pubmed-meshheading:14602203-Nitric Oxide Synthase, pubmed-meshheading:14602203-Nitric Oxide Synthase Type II, pubmed-meshheading:14602203-Recombinant Proteins, pubmed-meshheading:14602203-Superoxide Dismutase, pubmed-meshheading:14602203-Tumor Necrosis Factor-alpha, pubmed-meshheading:14602203-Up-Regulation, pubmed-meshheading:14602203-Virus Inactivation, pubmed-meshheading:14602203-Virus Replication

Active and inactive influenza virus induction of tumor necrosis factor-alpha and nitric oxide in J774.1 murine macrophages: modulation by interferon-gamma and failure to induce apoptosis.

Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't