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suck abstract from ncbi


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pmid1940351      J+Immunol 1991 ; 147 (10): 3507-13
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  • Influenza A virus infection of macrophages Enhanced tumor necrosis factor-alpha (TNF-alpha) gene expression and lipopolysaccharide-triggered TNF-alpha release #MMPMID1940351
  • Gong JH; Sprenger H; Hinder F; Bender A; Schmidt A; Horch S; Nain M; Gemsa D
  • J Immunol 1991[Nov]; 147 (10): 3507-13 PMID1940351show ga
  • We have previously shown that infection of macrophages by influenza A virus is capable of priming for a high TNF-alpha production in response to LPS. The present study was designed to examine in more detail TNF-alpha gene expression and TNF-alpha protein release of virus-infected, murine PU5-1.8 macrophages in the presence or absence of low and by itself rather inefficient concentrations of LPS (10 ng/ml). Although influenza A virus infection alone induced a massive TNF-alpha mRNA accumulation, translation into the bioactive TNF-alpha protein was low as intra- and extracellularly determined by bioassay, specific ELISA and Western blot. However, when LPS was added simultaneously or up to 4 h after infection, a high TNF-alpha production was initiated. The virus-induced TNF-alpha mRNA accumulation appeared to be due to both transcriptional and post-transcriptional changes: an enhanced TNF-alpha gene transcription as determined by nuclear run-on transcription assay and a markedly prolonged half-life of TNF-alpha mRNA as shown in actinomycin D-treated macrophages. These findings imply that influenza A virus may 1) either directly or indirectly stimulate TNF-alpha gene transcription activators or may interfere with labile transcription repressor proteins and 2) may stabilize TNF-alpha mRNA by delaying its degradation. Both mechanisms, taken together, prime influenza A virus-infected macrophages for a high TNF-alpha release in response to LPS which, as clinical cases show, may adversely affect patients with combined influenza A virus and bacterial infections.
  • |Animals[MESH]
  • |Cell Line[MESH]
  • |Gene Expression[MESH]
  • |In Vitro Techniques[MESH]
  • |Influenza A virus/*immunology[MESH]
  • |Lipopolysaccharides/immunology[MESH]
  • |Macrophages/*immunology[MESH]
  • |Mice[MESH]
  • |Orthomyxoviridae Infections/*immunology[MESH]
  • |RNA, Messenger/metabolism[MESH]
  • |Transcription, Genetic[MESH]


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