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No major role for the transcription factor NF-κB in bone marrow function during peritonitis in the mouse

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Abstract

Nuclear factor-kappa B (NF-κB) is a multipotent transcription factor that plays a pivotal role in immune reactions, inflammation, and possibly hematopoiesis as well. Mobilization of neutrophilic granulocytes during inflammation is a highly regulated process, but one that is incompletely understood. We studied the in vivo activity of NF-κB in mouse organs and cells, with a focus on bone marrow, during acute inflammation. NF-κB activity was studied in transgenic mice expressing a luciferase reporter expressed in a NF-κB activation-dependent fashion. Acute peritoneal inflammation was induced by lipopolysaccharide (LPS), the casein digest bacto-tryptone, or the insoluble polysaccharide zymosan. Organs were removed and blood, bone marrow, and peritoneal cells were separated using density gradient centrifugation. NF-κB activity in organ homogenates and cell lysates was quantified. These three inflammatory agents increased NF-κB activity to a variable extent within the inflamed peritoneal cavity, liver, and spleen, with LPS being the strongest stimulus. LPS, but not bacto-tryptone or zymosan, activated NF-κB in lung and bone marrow, the latter activity mainly observed in density fractions rich in immature bone marrow cells. NF-κB activation was prominent at 6 h after induction of peritonitis, fading at 24 h, as expected for an acute phase phenomenon. From this proof-of-principle study with luciferase reporter mice dependent on NF-κB activation, we suggest that, in steady-state mice, mobilization of bone marrow granulocytes to an inflammatory site can occur without discernible activation of NF-κB in bone marrow.

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Acknowledgments

We would like to thank Inger Strøm-Gundersen and Lene Gilen for their technical assistance. Grants were provided from the Norwegian Cancer Society, the Grethe Harbitz Legacy, the Legacy of Henrik Homan’s Minde, and Anders Jahre’s Foundation.

Conflict of interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Department of Physiology, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway

    Eirunn Knudsen, Arne Bøyum & Haakon Breien Benestad

  2. Department of Nutrition, Institute of Basic Medical Sciences, University of Oslo, P.O. Box 1046, Blindern, 0317, Oslo, Norway

    Harald Carlsen & Per Ole Iversen

  3. Department of Hematology, Oslo University Hospital, Rikshospitalet, Oslo, Norway

    Per Ole Iversen

Authors
  1. Eirunn Knudsen
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  2. Harald Carlsen
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  3. Arne Bøyum
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  4. Haakon Breien Benestad
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  5. Per Ole Iversen
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Correspondence to Per Ole Iversen.

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Knudsen, E., Carlsen, H., Bøyum, A. et al. No major role for the transcription factor NF-κB in bone marrow function during peritonitis in the mouse. Int J Hematol 100, 111–118 (2014). https://doi.org/10.1007/s12185-014-1598-7

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  • DOI: https://doi.org/10.1007/s12185-014-1598-7

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