Abstract
NF-kappaB is a regulatory protein of immune response genes and a candidate for targeting in immunosuppressive therapy. NF-kappaB proteins are formed from components of which p50 (NFkappaB1) is a subunit. By targeting p50 gene expression with specific antisense 3' phosphorothioate-oligodeoxynucleotides (3' PS-ODNs), an effect upon NF-kappaB regulation and immunoglobulin synthesis in murine B cells was achieved. A 49% decrease in p50 protein was induced by treatment of WEHI 231 B cells with p50 antisense 3' PS-ODNs and not by control 3' PS-ODNs. p50 antisense specifically reduced the expression of NF-kappaB by 51%, but not the transcription factor, Oct-1. In the BXSB murine model of autoimmunity, p50 antisense inhibited NF-kappaB expression and total IgM and IgG synthesis, but, more importantly, dsDNA antibodies were reduced 90%. These results validate the use of p50 antisense to reduce NF-kappaB expression and, by downregulating the immune response, has application in the treatment of autoimmune disorders.
References
Jan 1, 1978·Proceedings of the National Academy of Sciences of the United States of America·P C Zamecnik, M L Stephenson
Dec 11, 1992·Science·I KitajimaM Nerenberg
Aug 15, 1992·Proceedings of the National Academy of Sciences of the United States of America·T M WoolfC G Jennings
Apr 1, 1992·Journal of Autoimmunity·A D SteinbergM F Gourley
Apr 1, 1992·Clinical and Experimental Immunology·A KitaniH Nakamura
Jan 1, 1992·Annual Review of Pharmacology and Toxicology·S T Crooke
Dec 1, 1991·Pharmacology & Therapeutics·C A SteinL Yakubov
Jan 1, 1991·Antisense Research and Development·A M KriegA D Steinberg
Jan 1, 1991·Life Sciences·S AkhtarR L Juliano
Jan 1, 1991·Molecular and Cellular Biology·H P HohmannA P van Loon
Aug 28, 1990·Journal of Immunological Methods·W EmlenG Burdick
Aug 29, 1986·Cell·R Sen, D Baltimore
Nov 1, 1987·Proceedings of the National Academy of Sciences of the United States of America·M MatsukuraS Broder
Mar 11, 1983·Nucleic Acids Research·J D DignamR G Roeder
Sep 1, 1995·Immunity·T S Finco, A S Baldwin
Jun 1, 1995·Trends in Biotechnology·S Agrawal, S Akhtar
Jan 1, 1995·Antisense Research and Development·D G Spiller, D M Tidd
Oct 1, 1994·Cellular and Molecular Neurobiology·W Brysch, K H Schlingensiepen
Apr 6, 1995·Nature·A M KriegD M Klinman
Jan 27, 1995·Cell·W C ShaD Baltimore
Nov 24, 1994·Nature·R W Wagner
Jan 1, 1994·Annual Review of Immunology·P A Baeuerle, T Henkel
Nov 1, 1993·Proceedings of the National Academy of Sciences of the United States of America·K A HigginsR Narayanan
Jul 9, 1993·Journal of Medicinal Chemistry·J F MilliganJ C Martin
Aug 20, 1993·Science·C A Stein, Y C Cheng
Jun 1, 1993·Molecular and Cellular Biology·R NarayananC A Rosen
Citations
Feb 3, 2012·Inflammation Research : Official Journal of the European Histamine Research Society ... [et Al.]·Zhi-Chun Liu, Qiao-Ling Zhou
Oct 29, 2002·Cellular Signalling·Susanne BellKorbinian Brand
Jun 22, 1999·Toxicology and Applied Pharmacology·S A BellK Brand
Nov 6, 2009·Journal of Microencapsulation·Sanjay G GayakwadMartin J D'Souza
Apr 18, 2018·AAPS PharmSciTech·Ruhi V UbaleMartin J D'Souza
Jul 31, 2008·Journal of Microencapsulation·Nima AkhaveinMartin J D'souza
Jan 22, 2005·Annals of the New York Academy of Sciences·Sylvie DelhalleMarc Diederich