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 cells 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 cells 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.
No Reference information available - sign in for access.
No Citation information available - sign in for access.
No Supplementary Data.
No Article Media
Document Type: Research Article
Department of Host Defense and Biochemical Research, Juntendo University, Graduate School of Medicine, Tokyo 1138421, Japan
Institute of Physical and Theoretical Chemistry, University of Regensburg, D93053 Regensburg, Germany
Department of Microbiology, Juntendo University, Graduate School of Medicine, Tokyo 1138421, Japan
Department of Emergency and Disaster Medicine, Juntendo University, Graduate School of Medicine, Tokyo 1138421, Japan
Department of Clinical Laboratory Medicine, Juntendo University, Graduate School of Medicine, Tokyo 1138421, Japan
Publication date: January 1, 2017
More about this publication?
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.
- Editorial Board
- Information for Authors
- Submit a Paper
- Subscribe to this Title
- Information for Advertisers
- Terms & Conditions
- Ingenta Connect is not responsible for the content or availability of external websites