Chronic inflammation and susceptibility to bacterial infections in mice lacking the polypeptide (p)105 precursor (NF-kappaB1) but expressing p50

The Journal of Experimental Medicine
H IshikawaR Bravo

Abstract

The polypeptide (p)50 molecule, a subunit of nuclear factor (NF)-kappaB, is produced after proteolytic processing of the p105 precursor (NF-kappaB1). Although the p105 precursor has been postulated to play a role in the regulation of the Rel/NF-kappaB activity, its physiological relevance remains unclear. To investigate that, we generated mutant mice lacking the COOH terminal half of the p105 precursor, but expressing the p50 product (p105-/-). These mutant mice displayed an inflammatory phenotype composed of lymphocytic infiltration in lungs and liver, and an increased susceptibility to opportunistic infections. Enlargement of multiple lymph nodes, splenomegaly due to erythrocytic extramedullary hematopoiesis, and lymphoid hyperplasia were also observed in p105-/- mice. Cytokine production in p105-/- macrophages was severely impaired, whereas proliferative responses of p105-/- B cells were increased. T cell functions were only moderately impaired in mutant mice. Loss of p105 also led to enhanced constitutive p50 homodimer and inducible NF-kappaB activities in unstimulated and stimulated cells, respectively. As several genes regulated by Rel/NF-kappaB were upregulated in p105-/- thymus but downregulated in p105-/- macrophages, ...Continue Reading

References

May 1, 1992·Genes & Development·M KretzschmarR G Roeder
Nov 15, 1995·Genes & Development·I M VermaS Miyamoto
Jan 1, 1995·Advances in Immunology·E B Kopp, S Ghosh
Feb 24, 1995·Cell·D Thanos, T Maniatis
Jan 1, 1994·Annual Review of Cell Biology·U SiebenlistK Brown
Jan 1, 1994·Annual Review of Immunology·P A Baeuerle, T Henkel
Apr 15, 1994·Brain Research. Developmental Brain Research·X JiangT C Sacktor
Feb 15, 1994·Proceedings of the National Academy of Sciences of the United States of America·S C SunW C Greene
Dec 1, 1993·Trends in Genetics : TIG·T D Gilmore, P J Morin
Nov 1, 1993·Genes & Development·G J Nabel, I M Verma
Jun 1, 1993·Current Opinion in Cell Biology·H C Liou, D Baltimore
Jan 1, 1993·International Review of Cytology·M GrilliM J Lenardo
Jan 15, 1997·Genes & Development·E M SchwarzI M Verma
Jul 1, 1967·Proceedings of the Society for Experimental Biology and Medicine·M H PinedaM L Hopwood

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Citations

Jun 16, 2001·Journal of Cellular Biochemistry·W D Cornwell, R B Kirkpatrick
Mar 15, 2006·Cardiovascular Drugs and Therapy·Arno RuusaleppGuro Valen
Jan 22, 2004·Current Opinion in Immunology·Anne PuelJean-Laurent Casanova
Apr 23, 2004·Trends in Biochemical Sciences·Yumi Yamamoto, Richard B Gaynor
Jan 24, 2013·Mucosal Immunology·M Hedl, C Abraham
Dec 20, 2002·Nature·Carl Nathan
Dec 9, 2008·Nature Immunology·Srividya SriskantharajahSteven C Ley
May 12, 2004·Nature Reviews. Drug Discovery·Derek W GilroyAdriano G Rossi
Feb 14, 2006·Cell Death and Differentiation·M PasparakisM Schmidt-Supprian
May 18, 2011·Proceedings of the National Academy of Sciences of the United States of America·Jimmy L ZhaoDavid Baltimore
Sep 22, 1998·The Journal of Experimental Medicine·J D ChengR Bravo
Jan 10, 2002·Critical Care Medicine·Uwe Senftleben, Michael Karin
Sep 9, 2005·Current Opinion in Lipidology·Sofia XanthouleaMenno P J de Winther
Jul 5, 2002·Clinical Microbiology Reviews·Jorge Caamaño, Christopher A Hunter
Jun 27, 2012·Molecular and Cellular Biology·Huei-Ting YangSteven C Ley
Dec 17, 2002·Molecular and Cellular Biology·Valerie LangSteven C Ley
Jul 2, 2003·Molecular and Cellular Biology·S BeinkeS C Ley
Jul 15, 2003·American Journal of Respiratory and Critical Care Medicine·Joseph P MizgerdGeorge P Topulos
Sep 18, 2002·The Journal of Clinical Investigation·Brendan A HilliardYouhai H Chen
Nov 8, 2002·American Journal of Pharmacogenomics : Genomics-related Research in Drug Development and Clinical Practice·Yuti ChernajovskyPanagiotis S Kabouridis
Oct 12, 2000·Proceedings of the National Academy of Sciences of the United States of America·B J O'SullivanR Thomas
Apr 6, 2006·Proceedings of the National Academy of Sciences of the United States of America·Joerg SchreiberRichard A Young
Jun 6, 2006·Proceedings of the National Academy of Sciences of the United States of America·Leon Bernal-MizrachiLee Ratner
Sep 17, 2014·The Journal of Experimental Medicine·Emilie JacqueSteven C Ley
Aug 22, 2008·Digestive Diseases and Sciences·Tamas SzamosiHajnalka Andrikovics
Nov 19, 2013·Immunologic Research·Rajeshree PujariNoula Shembade
Nov 30, 2005·International Journal of Immunogenetics·M E A BormG Bouma
Jan 21, 2006·Immunology·Ruaidhrí J CarmodyYouhai H Chen
Jul 30, 2011·EMBO Reports·Shin-Heng ChiouDavid M Spencer
Oct 29, 2015·Mediators of Inflammation·Ting LiuHeping Yang
May 8, 2015·Nature Communications·Rachel TsuiAlexander Hoffmann

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Methods Mentioned

BETA
ubiquitination
Flow Cytometry
light microscopy
Assay
lavage
electrophoretic mobility shift assay
PCR
PMA
ELISA

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