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Neutrophil extracellular traps induce IL-1β production by macrophages in combination with lipopolysaccharide

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Upon exposure to invading microorganisms, neutrophils undergo NETosis, a recently identified type of programmed cell death, and release neutrophil extracellular traps (NETs). NETs are described as an antimicrobial mechanism, based on the fact that NETs can trap microorganisms and exhibit bactericidal activity through the action of NETassociated components. In contrast, the components of NETs have been recognized as damageassociated molecular pattern molecules (DAMPs), which trigger inflammatory signals to induce cell death, inflammation and organ failure. In the present study, to clarify the effect of NETs on cytokine production by macrophages, mouse macrophagelike J774┬ácells were treated with NETs in combination with lipopolysaccharide (LPS) as a constituent of pathogenassociated molecular patterns. The results revealed that NETs significantly induced the production of interleukin (IL)1β by J774┬ácells in the presence of LPS. Notably, the NET/LPSinduced IL1β production was inhibited by both caspase1 and caspase8 inhibitors. Furthermore, nucleases and serine protease inhibitors but not antihistone antibodies significantly inhibited the NET/LPSinduced IL1β production. Moreover, we confirmed that caspase1 and caspase8 were activated by NETs/LPS, and the combination of LPS, DNA and neutrophil elastase induced IL1β production in reconstitution experiments. These observations indicate that NETs induce the production of IL1β by J774 macrophages in combination with LPS via the caspase1 and caspase8 pathways, and NETassociated DNA and serine proteases are involved in NET/LPSinduced IL1β production as essential components.
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Document Type: Research Article

Affiliations: 1: Department of Host Defense and Biochemical Research, Juntendo University, Graduate School of Medicine, Tokyo 1138421, Japan 2: Institute of Physical and Theoretical Chemistry, University of Regensburg, D93053 Regensburg, Germany 3: Department of Microbiology, Juntendo University, Graduate School of Medicine, Tokyo 1138421, Japan 4: Department of Emergency and Disaster Medicine, Juntendo University, Graduate School of Medicine, Tokyo 1138421, Japan 5: Department of Clinical Laboratory Medicine, Juntendo University, Graduate School of Medicine, Tokyo 1138421, Japan

Publication date: January 1, 2017

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  • The International Journal of Molecular Medicine is a monthly, peer-reviewed journal devoted to the publication of high quality studies related to the molecular mechanisms of human disease. The journal welcomes research on all aspects of molecular and clinical research, ranging from biochemistry to immunology, pathology, genetics, human genomics, microbiology, molecular pathogenesis, molecular cardiology, molecular surgery and molecular psychology.

    The International Journal of Molecular Medicine aims to provide an insight for researchers within the community in regard to developing molecular tools and identifying molecular targets for the diagnosis and treatment of a diverse number of human diseases.
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