Reduced infiltration and increased apoptosis of leukocytes at sites of inflammation by systemic administration of a membrane-permeable IkappaBalpha repressor

Arthritis and Rheumatism
Nathan M BlackwellPanagiotis S Kabouridis

Abstract

NF-kappaB activation is associated with several inflammatory disorders, including rheumatoid arthritis (RA), making this family of transcription factors a good target for the development of antiinflammatory treatments. Although inhibitors of the NF-kappaB pathway are currently available, their specificity has not been adequately determined. IkappaBalpha is a physiologic inhibitor of NF-kappaB and a potent repressor experimentally when expressed in a nondegradable form. We describe here a novel means for specifically regulating NF-kappaB activity in vivo by administering a chimeric molecule comprising the super-repressor IkappaBalpha (srIkappaBalpha) fused to the membrane-transducing domain of the human immunodeficiency virus Tat protein (Tat-srIkappaBalpha). The Wistar rat carrageenan-induced pleurisy model was used to assess the effects of in vivo administration of Tat-srIkappaBalpha on leukocyte infiltration and on cytokine and chemokine production. Systemic administration of Tat-srIkappaBalpha diminished infiltration of leukocytes into the site of inflammation. Analysis of the recruited inflammatory cells confirmed uptake of the inhibitor and reduction of the NF-kappaB activity. These cells exhibited elevated caspase activit...Continue Reading

References

Nov 1, 1994·British Journal of Pharmacology·A TomlinsonD A Willoughby
Jan 18, 1994·Proceedings of the National Academy of Sciences of the United States of America·S FawellJ Barsoum
Jan 1, 1996·Annual Review of Immunology·A S Baldwin
Dec 1, 1995·Arthritis and Rheumatism·M L HandelE M Gravallese
Nov 13, 1998·Proceedings of the National Academy of Sciences of the United States of America·A V MiagkovS S Makarov
Apr 17, 1999·European Journal of Pharmacology·F D'AcquistoR Carnuccio
May 14, 1999·Trends in Pharmacological Sciences·A A PieperS H Snyder
Jun 17, 1999·Nature Medicine·D W GilroyD A Willoughby
Dec 1, 1999·Cell Death and Differentiation·D W Nicholson
Jun 3, 2000·Annual Review of Immunology·M Karin, Y Ben-Neriah
Nov 14, 2000·Molecular Medicine Today·S S Makarov
Dec 20, 2000·The Journal of Immunology : Official Journal of the American Association of Immunologists·C GeorganasR M Pope
Jan 3, 2001·The Journal of Clinical Investigation·A S Baldwin
Jan 3, 2001·The Journal of Clinical Investigation·P P Tak, G S Firestein
Feb 13, 2001·The Journal of Clinical Investigation·Y Yamamoto, R B Gaynor
Jul 24, 2001·The Journal of Immunology : Official Journal of the American Association of Immunologists·E AlcamoD Baltimore
Aug 18, 2001·Arthritis and Rheumatism·P P TakG S Firestein
Dec 1, 2001·Nature Medicine·T LawrenceD A Willoughby
Jan 22, 2002·The Journal of Biological Chemistry·Andreas BirbachJohannes A Schmid
May 22, 2002·Current Opinion in Pharmacology·Amy K RoshakSimon M Blake
Aug 24, 2002·The Journal of Immunology : Official Journal of the American Association of Immunologists·Panagiotis S KabouridisToby Lawrence
Sep 24, 2002·The Journal of Immunology : Official Journal of the American Association of Immunologists·Susana Castro-AlcarazIvana Vancurova
Jan 28, 2003·Journal of Molecular Biology·Giichi TakaesuRichard B Gaynor
Apr 18, 2003·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Peter J ElliottWolf-Henning Boehncke
Jul 9, 2003·The Journal of Immunology : Official Journal of the American Association of Immunologists·KeQing WangJanet M Lord
Oct 18, 2003·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Derek W GilroyToby Lawrence
Oct 24, 2003·Trends in Biotechnology·Panagiotis S Kabouridis
Jan 7, 2004·Nature Reviews. Drug Discovery·Michael KarinQ May Wang

❮ Previous
Next ❯

Citations

Aug 1, 2008·Cellular and Molecular Life Sciences : CMLS·J S Orange, M J May
Oct 15, 2008·International Reviews of Immunology·Jorge A Roman-Blas, Sergio A Jimenez
Jul 11, 2008·Expert Opinion on Biological Therapy·Chris JacksonMeilang Xue
Feb 22, 2005·Advanced Drug Delivery Reviews·Bhawna GuptaVladimir P Torchilin
Mar 16, 2016·Journal of Tissue Engineering·Francesca TaraballiEnnio Tasciotti
Jan 1, 2013·Cells·Driss El Kebir, János G Filep
Oct 4, 2014·Journal of Cell Death·Jenna M McCracken, Lee-Ann H Allen
Aug 31, 2004·Arthritis and Rheumatism·Gary S Firestein
Dec 10, 2008·FEBS Letters·Nasser M MalikPanagiotis S Kabouridis
Jun 19, 2008·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Ellen Niederberger, Gerd Geisslinger
Sep 28, 2013·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Apostolos KoutsokerasDavid Gould
Aug 29, 2006·The Journal of Pharmacology and Experimental Therapeutics·Soledad NegrottoMirta Schattner
Jul 6, 2007·Current Opinion in Pharmacology·David J Gould, Yuti Chernajovsky
Dec 23, 2008·Biochimica Et Biophysica Acta·Apostolos Koutsokeras, Panagiotis S Kabouridis

❮ Previous
Next ❯

Related Concepts

Related Feeds

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis

Caspases in Metabolic Diseases

Caspases, the family of cysteine proteases are involved in programmed cell death, but their role in metabolic diseases, inflammation and immunity has been of interested. Discover the latest research on caspases in metabolic diseases here.

Anti-inflammatory Treatments

A drug or substance that reduces inflammation (redness, swelling, and pain) in the body. Anti-inflammatory agents block certain substances in the body that cause inflammation and swelling. Discover the latest research on anti-inflammatory treatments here

Apoptotic Caspases

Apoptotic caspases belong to the protease enzyme family and are known to play an essential role in inflammation and programmed cell death. Here is the latest research.