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Synergistic action of pro‐inflammatory agents: cellular and molecular aspects
Author(s) -
Paludan Søren R.
Publication year - 2000
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1002/jlb.67.1.18
Subject(s) - biology , microbiology and biotechnology , proinflammatory cytokine , transcription factor , stat protein , tumor necrosis factor alpha , signal transduction , inflammation , lipopolysaccharide , cytokine , immune system , activator (genetics) , immunology , gene , biochemistry , stat3
Generation of an inflammatory response is a complex process involving multiple factors acting in parallel and in concert. Viruses, parasites, and bacteria, particularly lipopolysaccharide (LPS), a component of the cell wall of gram‐negative bacteria, act cooperatively with the cytokine interferon (IFN)‐γ to induce many of the genes involved in inflammation. In addition, these components synergistically induce secretion of tumor necrosis factor α (TNF‐α), which also synergizes strongly with IFN‐γ. The molecular mechanisms underlying the synergistic gene induction discussed in this review involve cooperative activation of transcription factors. IFN‐γ‐activated signal transducer and activator of transcription 1 and interferon regulatory factor‐1 function synergistically with nuclear factor κB activated by LPS and TNF‐α. In addition, cross‐talk between the signal transduction pathways upstream of the activation of the transcription factors contributes to generation of the synergistic action. Cooperative activity of proinflammatory agents profoundly influences the immune response to infections and the efficiency of cellular clearance mechanisms. J. Leukoc. Biol. 67: 18–25; 2000.